Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Nature Genetics volume 52, pages 482–493 (2020)Cite this article

Subjects

Abstract

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Study design and tissue-level associations.
Fig. 2: Association of selected brain-related traits with cell types from the entire nervous system.
Fig. 3: Replication of associations between cell type and trait in mouse datasets.
Fig. 4: Human replication of associations between cell type and trait.
Fig. 5: Enrichment of Parkinson’s disease differentially expressed genes in cell types from the substantia nigra.

Similar content being viewed by others

Data availability

All single-cell expression data are publicly available. Most summary statistics used in this study are publicly available. The migraine GWAS60 can be obtained by contacting the authors of that study. The full Parkinson’s disease summary statistics from 23andMe can be obtained under an agreement that protects the privacy of 23andMe research participants (https://research.23andme.com/collaborate/#publication). The 10,000 most associated SNPs from the 23andMe cohort are available in Supplementary Table 12.

Code availability

The code used to generate these results is available at https://github.com/jbryois/scRNA_disease. An R package for performing cell-type enrichments using MAGMA is also available from https://github.com/NathanSkene/MAGMA_Celltyping.

References

  1. Pardiñas, A. F. et al. Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat. Genet. 50, 381–389 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Lee, J. J., Wedow, R. & Okbay Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nat. Genet. 50, 1112–1121 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nagel, M. et al. Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways. Nat. Genet. 50, 920–927 (2018).

    Article  CAS  PubMed  Google Scholar 

  4. Yengo, L. et al. Meta-analysis of genome-wide association studies for height and body mass index in ∼700000 individuals of European ancestry. Hum. Mol. Genet. 27, 3641–3649 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maurano, M. T. et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337, 1190–1195 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Akbarian, S. et al. The PsychENCODE project. Nat. Neurosci. 18, 1707–1712 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aguet, F. et al. Genetic effects on gene expression across human tissues. Nature 550, 204–213 (2017).

    Article  Google Scholar 

  8. Roadmap Epigenomics Consortium et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–329 (2015).

    Article  PubMed Central  CAS  Google Scholar 

  9. Ongen, H. et al. Estimating the causal tissues for complex traits and diseases. Nat. Genet. 49, 1676–1683 (2017).

    Article  CAS  PubMed  Google Scholar 

  10. Skene, N. G. & Grant, S. G. N. Identification of vulnerable cell types in major brain disorders using single cell transcriptomes and expression weighted cell type enrichment. Front. Neurosci. 10, 1–11 (2016).

    Article  Google Scholar 

  11. Skene, N. G. et al. Genetic identification of brain cell types underlying schizophrenia. Nat. Genet. 50, 825–833 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Finucane, H. K. et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet. 50, 621–629 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Calderon, D. et al. Inferring relevant cell types for complex traits by using single-cell gene expression. Am. J. Hum. Genet. 101, 686–699 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Savage, J. E. et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat. Genet. 50, 912–919 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Coleman, J. R. I. et al. Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals. Mol. Psychiatry 24, 182–197 (2019).

    Article  CAS  PubMed  Google Scholar 

  16. Jansen, I. E. et al. Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. 51, 404–413 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Nalls, M. A. et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 18, 1091–1102 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11, 1–19 (2015).

    Article  CAS  Google Scholar 

  19. Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 1228–1235 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jevtic, S., Sengar, A. S., Salter, M. W. & McLaurin, J. A. The role of the immune system in Alzheimer disease: etiology and treatment. Ageing Res. Rev. 40, 84–94 (2017).

    Article  CAS  PubMed  Google Scholar 

  21. Kunkle, B. W. et al. Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 51, 414–430 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. O’Leary, D. H. et al. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N. Engl. J. Med. 340, 14–22 (1999).

    Article  PubMed  Google Scholar 

  23. Zeisel, A. et al. Molecular architecture of the mouse nervous system. Cell 174, 999–1014.e22 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Anttila, V. et al. Analysis of shared heritability in common disorders of the brain. Science 360, (2018).

  25. Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e17 (2017).

    Article  CAS  PubMed  Google Scholar 

  26. Braak, H. et al. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging 24, 197–211 (2003).

    Article  PubMed  Google Scholar 

  27. Sulzer, D. & Surmeier, D. J. Neuronal vulnerability, pathogenesis, and Parkinson’s disease. Mov. Disord. 28, 41–50 (2013).

    Article  CAS  PubMed  Google Scholar 

  28. Poewe, W. et al. Parkinson disease. Nat. Rev. Dis. Primers 3, 17013 (2017).

    Article  PubMed  Google Scholar 

  29. Halliday, G. M. et al. Neuropathology of immunohistochemically identified brainstem neurons in Parkinson’s disease. Ann. Neurol. 27, 373–385 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Delaville, C., de Deurwaerdère, P. & Benazzouz, A. Noradrenaline and Parkinson’s disease. Front. Syst. Neurosci. https://doi.org/10.3389/fnsys.2011.00031 (2011).

  31. Rinne, J. O., Ma, S. Y., Lee, M. S., Collan, Y. & Röyttä, M. Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson’s disease is related to disability of the patients. Parkinsonism Relat. Disord. 14, 553–557 (2008).

    Article  Google Scholar 

  32. Braak, H., Rüb, U., Gai, W. P. & Del Tredici, K. Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm. 110, 517–536 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Liddle, R. A. Parkinson’s disease from the gut. Brain Res. 1693, 201–206 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Saunders, A. et al. Molecular diversity and specializations among the cells of the adult mouse brain. Cell 174, 1015–1030.e16 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Habib, N. et al. Massively parallel single-nucleus RNA-seq with DroNc-seq. Nat. Methods 14, 955 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lake, B. B. et al. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain. Nat. Biotechnol. 36, 70–80 (2018).

    Article  CAS  PubMed  Google Scholar 

  37. Lesnick, T. G. et al. A genomic pathway approach to a complex disease: axon guidance and Parkinson disease. PLoS Genet. 3, 0984–0995 (2007).

    Article  CAS  Google Scholar 

  38. Moran, L. B. et al. Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson’s disease. Neurogenetics 7, 1–11 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Kannarkat, G. T., Boss, J. M. & Tansey, M. G. The role of innate and adaptive immunity in Parkinson’s disease. J. Parkinsons Dis. 3, 493–514 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gagliano, S. A. et al. Genomics implicates adaptive and innate immunity in Alzheimer’s and Parkinson’s diseases. Ann. Clin. Transl. Neurol. 3, 924–933 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dijkstra, A. A. et al. Evidence for immune response, axonal dysfunction and reduced endocytosis in the substantia nigra in early stage Parkinson’s disease. PLoS ONE 10, e0128651 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Lake, B. B. et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science 352, 1586–1590 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sathyamurthy, A. et al. Massively parallel single nucleus transcriptional profiling defines spinal cord neurons and their activity during behavior. Cell Rep. 22, 2216–2225 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lake, B. B. et al. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA. Sci. Rep. 7, 6031 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Caspi, A. et al. The p factor: one general psychopathology factor in the structure of psychiatric disorders? Clin. Psychol. Sci. 2, 119–137 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sullivan, P. F. & Geschwind, D. H. Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell 177, 162–183 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Reynolds, R. H. et al. Moving beyond neurons: the role of cell type-specific gene regulation in Parkinson’s disease heritability. NPJ Parkinsons Dis. 5, 6 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Singaram, C. et al. Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 346, 861–864 (1995).

    Article  CAS  PubMed  Google Scholar 

  49. Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E. & Ikuta, F. Lewy bodies in the enteric nervous system in Parkinson’s disease. Arch. Histol. Cytol. 52, 191–194 (1989).

    Article  PubMed  Google Scholar 

  50. Stokholm, M. G., Danielsen, E. H., Hamilton-Dutoit, S. J. & Borghammer, P. Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann. Neurol. 79, 940–949 (2016).

    Article  CAS  PubMed  Google Scholar 

  51. Svensson, E. et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann. Neurol. 78, 522–529 (2015).

    Article  PubMed  Google Scholar 

  52. Gilman, S. et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology 71, 670–676 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Nalls, M. A. et al. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson’s disease. Nat. Genet. 46, 989–993 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Wakabayashi, K., Hayashi, S., Yoshimoto, M., Kudo, H. & Takahashi, H. NACP/α-synuclein-positive filamentous inclusions in astrocytes and oligodendrocytes of Parkinson’s disease brains. Acta Neuropathol. 99, 14–20 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Seidel, K. et al. The brainstem pathologies of Parkinson’s disease and dementia with Lewy bodies. Brain Pathol. 25, 121–135 (2015).

    Article  PubMed  Google Scholar 

  56. Stahl, E. A. et al. Genome-wide association study identifies 30 loci associated with bipolar disorder. Nat. Genet. 51, 793–803 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Perry, J. R. B. et al. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature 514, 92–97 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Grove, J. et al. Identification of common genetic risk variants for autism spectrum disorder. Nat. Genet. 51, 431–444 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gormley, P. et al. Meta-analysis of 375,000 individuals identifies 38 susceptibility loci for migraine. Nat. Genet. 48, 1296 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Van Rheenen, W. et al. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis. Nat. Genet. 48, 1043–1048 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Demontis, D. et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat. Genet. 51, 63–75 (2019).

    Article  CAS  PubMed  Google Scholar 

  63. Day, F. R. et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat. Genet. 47, 1294–1303 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nelson, C. P. et al. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat. Genet. 49, 1385–1391 (2017).

    Article  CAS  PubMed  Google Scholar 

  65. Wheeler, E. et al. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations. PLoS Med. 14, 1–30 (2017).

    Article  Google Scholar 

  66. Hibar, D. P. et al. Novel genetic loci associated with hippocampal volume. Nat. Commun. 8, 13624 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. de Lange, K. M. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 49, 256–261 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Adams, H. H. H. et al. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat. Neurosci. 19, 1569–1582 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Malik, R. et al. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes. Nat. Genet. 50, 524–537 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Scott, R. A. et al. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes 66, 2888–2902 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shungin, D. et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 518, 187–196 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Watson, H. J. et al. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nat. Genet. 51, 1207–1214 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190–2191 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236–1241 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Auton, A. et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).

    Article  PubMed  CAS  Google Scholar 

  76. Watanabe, K., Umićević Mirkov, M., de Leeuw, C. A., van den Heuvel, M. P. & Posthuma, D. Genetic mapping of cell type specificity for complex traits. Nat. Commun. 10, 3222 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cajigas, I. J. et al. The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron 74, 453–466 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Alexa, A. & Rahnenfuhrer, J. topGO: enrichment analysis for Gene Ontology v.2.36 (2016).

  79. Gautier, L., Cope, L., Bolstad, B. M. & Irizarry, R. A. Affy - analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20, 307–315 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat. Protoc. 4, 1184–1191 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

J.B. was funded by a grant from the Swiss National Science Foundation (P400PB_180792). N.G.S. was supported by the Wellcome Trust (108726/Z/15/Z). N.G.S. and L.B. performed part of the work at the Systems Genetics of Neurodegeneration summer school funded by BMBF as part of the e:Med programme (FKZ 01ZX1704). J.H.-L. was funded by the Swedish Research Council (Vetenskapsrådet, award 2014-3863), StratNeuro, the Wellcome Trust (108726/Z/15/Z) and the Swedish Brain Foundation (Hjärnfonden). P.F.S. was supported by the Swedish Research Council (Vetenskapsrådet, award D0886501), the Horizon 2020 Program of the European Union (COSYN, RIA grant agreement no. 610307) and US NIMH (U01 MH109528 and R01 MH077139). E.A. was supported by the Swedish Research Council (VR 2016-01526), Swedish Foundation for Strategic Research (SLA SB16-0065), Karolinska Institutet (SFO Strat. Regen., Senior grant 2018), Cancerfonden (CAN 2016/572), Hjärnfonden (FO2017-0059) and Chen Zuckeberg Initiative: Neurodegeneration Challenge Network (2018-191929-5022). C.M.B. acknowledges funding from the Swedish Research Council (Vetenskapsrådet, award: 538-2013-8864) and the Klarman Family Foundation. This work is supported by the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. We thank the research participants from 23andMe and other cohorts for their contribution to this study.

Author information

Author notes

  1. These authors contributed equally: Julien Bryois, Nathan G. Skene.

Authors and Affiliations

  1. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Julien Bryois, Julien Bryois, Cynthia Bulik, Christopher Hübel, Anders Juréus, Mikael Landén, Virpi Leppä, Paul Lichtenstein, Nancy Pedersen, Patrick Sullivan, Shuyang Yao, Nancy Pedersen, Cynthia M. Bulik & Patrick F. Sullivan

  2. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

    Nathan G. Skene, Ernest Arenas & Jens Hjerling-Leffler

  3. UCL Institute of Neurology, Queen Square, London, UK

    Nathan G. Skene

  4. Division of Brain Sciences, Department of Medicine, Imperial College, London, UK

    Nathan G. Skene & Zijing Liu

  5. UK Dementia Research Institute at Imperial College, London, UK

    Nathan G. Skene & Zijing Liu

  6. Danish Headache Center, Dept of Neurology, Copenhagen University Hospital, Glostrup, Denmark

    Thomas Folkmann Hansen, Lisette J. A. Kogelman, Thomas Folkmann Hansen & Lisette J. A. Kogelman

  7. Institute of Biological Psychiatry, Copenhagen University Hospital MHC Sct Hans, Roskilde, Denmark

    Thomas Folkmann Hansen

  8. Novo Nordic Foundations Center for Protein Research, Copenhagen University, Copenhagen, Denmark

    Thomas Folkmann Hansen

  9. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Hunna J. Watson, Jessica Baker, Cynthia Bulik, Maria La Via, Melissa Munn-Chernoff, Garret Stuber, Laura Thornton, Hunna Watson, Zeynep Yilmaz, Stephanie Zerwas & Cynthia M. Bulik

  10. School of Psychology, Curtin University, Perth, Western Australia, Australia

    Hunna J. Watson & Hunna Watson

  11. Division of Paediatrics, School of Medicine, The University of Western Australia, Perth, Western Australia, Australia

    Hunna J. Watson & Hunna Watson

  12. Department of Psychiatry, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Leo Brueggeman

  13. Institute of Psychiatry, MRC Social, Genetic and Developmental Psychiatry Centre, King’s College London, London, UK

    Gerome Breen, Jonathan Coleman, Anne Farmer, Héléna Gaspar, Sietske Helder, Christopher Hübel, Gursharan Kalsi, Peter McGuffin, Kirstin Purves, Marion Roberts, Ulrike Schmidt, Janet Treasure & Gerome Breen

  14. National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK

    Gerome Breen, Jonathan Coleman, Héléna Gaspar & Gerome Breen

  15. Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA

    Cynthia Bulik & Cynthia M. Bulik

  16. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    James Crowley, Paola Giusti-Rodríquez, Patrick Sullivan, Jin Szatkiewicz, Zeynep Yilmaz & Patrick F. Sullivan

  17. Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands

    Roger Adan, Martien Kas, Bochao Danae Lin, Jurjen Luykx & Roel Ophoff

  18. Center for Eating Disorders Rintveld, Altrecht Mental Health Institute, Zeist, the Netherlands

    Roger Adan, Unna Danner & Annemarie van Elburg

  19. Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

    Roger Adan & Mikael Landén

  20. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Lars Alfredsson

  21. Department of Behavioral Medicine, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan

    Tetsuya Ando

  22. NORMENT KG Jebsen Centre, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway

    Ole Andreassen & Morten Mattingsdal

  23. BioRealm, LLC, Walnut, CA, USA

    Andrew Bergen

  24. Oregon Research Institute, Eugene, OR, USA

    Andrew Bergen

  25. Department of Psychiatry, Center for Neurobiology and Behavior, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Wade Berrettini

  26. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    Andreas Birgegård, James Crowley, Manuel Mattheisen & Claes Norring

  27. Center for Psychiatry Research, Stockholm Health Care Services, Stockholm City Council, Stockholm, Sweden

    Andreas Birgegård, Manuel Mattheisen & Claes Norring

  28. Christchurch Health and Development Study, University of Otago, Christchurch, New Zealand

    Joseph Boden & L. John Horwood

  29. Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany

    Ilka Boehm, Stefan Ehrlich, Franziska Ritschel & Esther Walton

  30. INSERM U894, Centre of Psychiatry and Neuroscience, Paris, France

    Claudette Boni, Philip Gorwood, Jacques Pantel & Nicolas Ramoz

  31. Wellcome Sanger Institute, Hinxton, Cambridge, UK

    Vesna Boraska Perica, Christopher Franklin, Konstantinos Hatzikotoulas, Laura Huckins, Ioanna Tachmazidou & Eleftheria Zeggini

  32. Department of Medical Biology, School of Medicine, University of Split, Split, Croatia

    Vesna Boraska Perica

  33. The Center for Eating Disorders at Sheppard Pratt, Baltimore, MD, USA

    Harry Brandt & Steven Crawford

  34. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany

    Katharina Buehren, Beate Herpertz-Dahlmann & Jochen Seitz

  35. Klinikum Frankfurt/Oder, Frankfurt, Germany

    Roland Burghardt

  36. Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padua, Italy

    Matteo Cassina, Maurizio Clementi & Monica Forzan

  37. Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland

    Sven Cichon, Andreas Forstner & Stefan Herms

  38. Life Sciences Institute and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Roger Cone

  39. Department of Emergency Psychiatry and Post-Acute Care, CHRU Montpellier, University of Montpellier, Montpellier, France

    Philippe Courtet & Sébastien Guillaume

  40. Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA

    Scott Crow

  41. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Oliver Davis

  42. School of Social and Community Medicine, University of Bristol, Bristol, UK

    Oliver Davis

  43. Department of Psychosomatic Medicine and Psychotherapy, Hannover Medical School, Hannover, Germany

    Martina de Zwaan

  44. Department of Nutrition and Dietetics, Harokopio University, Athens, Greece

    George Dedoussis & Ioanna Ntalla

  45. Department of Neurosciences, University of Padova, Padua, Italy

    Daniela Degortes, Angela Favaro & Elena Tenconi

  46. College of Nursing, Seattle University, Seattle, WA, USA

    Janiece DeSocio

  47. Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA

    Danielle Dick

  48. Department of Psychiatry, Athens University Medical School, Athens University, Athens, Greece

    Dimitris Dikeos

  49. L’institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France

    Christian Dina

  50. L’institut du thorax, CHU Nantes, Nantes, France

    Christian Dina

  51. Department of Psychiatric Genetics, Poznań University of Medical Sciences, Poznań, Poland

    Monika Dmitrzak-Weglarz

  52. Barcelona Institute of Science and Technology, Barcelona, Spain

    Elisa Docampo Martinez, Geòrgia Escaramís, Xavier Estivill & Monica Gratacos Mayora

  53. Universitat Pompeu Fabra, Barcelona, Spain

    Elisa Docampo Martinez, Geòrgia Escaramís, Xavier Estivill & Monica Gratacos Mayora

  54. Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

    Elisa Docampo Martinez, Geòrgia Escaramís, Xavier Estivill & Monica Gratacos Mayora

  55. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA

    Laramie Duncan

  56. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany

    Karin Egberts

  57. Estonian Genome Center, University of Tartu, Tartu, Estonia

    Tõnu Esko, Krista Fischer, Katrin Mannik, Andres Metspalu & Tonu Esko

  58. Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA

    Tõnu Esko, Aarno Palotie & Aarno Palotie

  59. Genomics and Disease, Bioinformatics and Genomics Programme, Centre for Genomic Regulation, Barcelona, Spain

    Xavier Estivill

  60. Department of Psychiatry, University Hospital of Bellvitge –IDIBELL and CIBERobn, Barcelona, Spain

    Fernando Fernández-Aranda & Susana Jiménez-Murcia

  61. Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain

    Fernando Fernández-Aranda & Susana Jiménez-Murcia

  62. Department of Psychiatry and Psychotherapy, Ludwig‐Maximilians‐University (LMU), Munich, Germany

    Manfred Fichter & Dan Rujescu

  63. Schön Klinik Roseneck affiliated with the Medical Faculty of the University of Munich (LMU), Munich, Germany

    Manfred Fichter

  64. Department of Child and Adolescent Psychiatry, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Manuel Föcker, Johanna Giuranna, Johannes Hebebrand & Anke Hinney

  65. Department of Cancer, Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic

    Lenka Foretova & Marie Navratilova

  66. Institute of Human Genetics, University of Bonn School of Medicine & University Hospital Bonn, Bonn, Germany

    Andreas Forstner

  67. Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany

    Andreas Forstner

  68. Department of Psychiatry (UPK), University of Basel, Basel, Switzerland

    Andreas Forstner

  69. Department of Biomedicine, University of Basel, Basel, Switzerland

    Andreas Forstner & Stefan Herms

  70. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    Steven Gallinger

  71. Department of Psychiatry, Psychotherapy and Psychosomatics, Martin Luther University of Halle-Wittenberg, Halle, Germany

    Ina Giegling & Dan Rujescu

  72. 1st Psychiatric Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece

    Fragiskos Gonidakis

  73. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

    Scott Gordon, Katherine Kirk, Nicholas Martin, Sarah Medland, Grant Montgomery, Catherine Olsen, Richard Parker & David Whiteman

  74. CMME (Groupe Hospitalier Sainte-Anne), Paris Descartes University, Paris, France

    Philip Gorwood

  75. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Jakob Grove & Manuel Mattheisen

  76. The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark

    Jakob Grove, Janne Larsen, Preben Bo Mortensen & Liselotte Petersen

  77. Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark

    Jakob Grove

  78. Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark

    Jakob Grove

  79. Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Yiran Guo, Hakon Hakonarson & Dong Li

  80. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Hakon Hakonarson

  81. Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA

    Katherine Halmi

  82. Department of Medical and Molecular Genetics, King’s College London, Guy’s Hospital, London, UK

    Ken Hanscombe

  83. Department of Adult Psychiatry, Poznań University of Medical Sciences, Poznań, Poland

    Joanna Hauser

  84. Zorg op Orde, Leidschendam, the Netherlands

    Sietske Helder

  85. Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia

    Anjali Henders & Grant Montgomery

  86. Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany

    Wolfgang Herzog

  87. Department of Psychiatry, and Genetics and Genomics Sciences, Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Laura Huckins & Dalila Pinto

  88. Biological Psychiatry Laboratory, McLean Hospital/Harvard Medical School, Boston, MA, USA

    James Hudson

  89. Eating Disorders Unit, Parklandklinik, Bad Wildungen, Germany

    Hartmut Imgart

  90. Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, Isehara, Japan

    Hidetoshi Inoko

  91. Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic

    Vladimir Janout

  92. Eating Recovery Center, Denver, CO, USA

    Craig Johnson

  93. Department of Psychological Medicine, University of Otago, Christchurch, New Zealand

    Jennifer Jordan

  94. Canterbury District Health Board, Christchurch, New Zealand

    Jennifer Jordan

  95. Rheumatology Research Group, Vall d’Hebron Research Institute, Barcelona, Spain

    Antonio Julià & Sara Marsal

  96. Department of Psychiatry, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Deborah Kaminská & Hana Papezova

  97. Center for Addiction and Mental Health, Department of Psychiatry, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Allan Kaplan & James Kennedy

  98. Department of Public Health, University of Helsinki, Helsinki, Finland

    Jaakko Kaprio, Anna Keski-Rahkonen, Anu Raevuori & Jaakko Kaprio

  99. Institute for Molecular Medicine Finland, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland

    Jaakko Kaprio, Aarno Palotie, Elisabeth Widen, Jaakko Kaprio & Aarno Palotie

  100. Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland

    Leila Karhunen

  101. Eating Disorders Unit, Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria

    Andreas Karwautz & Gudrun Wagner

  102. Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, the Netherlands

    Martien Kas

  103. Department of Psychiatry, University of California San Diego, San Diego, CA, USA

    Walter Kaye

  104. Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand

    Martin Kennedy

  105. Health Services Research Unit, University of Aberdeen, Aberdeen, UK

    Kirsty Kiezebrink

  106. Department of Psychiatry, Seoul Paik Hospital, Inje University, Seoul, Korea

    Youl-Ri Kim

  107. Rheumatology Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden

    Lars Klareskog & Leonid Padyukov

  108. Department of Psychology, Michigan State University, East Lansing, MI, USA

    Kelly Klump

  109. Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway

    Gun Peggy Knudsen & Ted Reichborn-Kjennerud

  110. National Centre for Register-Based Research, Aarhus BSS, Aarhus University, Aarhus, Denmark

    Janne Larsen, Preben Bo Mortensen & Liselotte Petersen

  111. Centre for Integrated Register-based Research (CIRRAU), Aarhus University, Aarhus, Denmark

    Janne Larsen, Preben Bo Mortensen & Liselotte Petersen

  112. Department of Clinical Science, K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), University of Bergen, Bergen, Norway

    Stephanie Le Hellard

  113. Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway

    Stephanie Le Hellard

  114. Department of Clinical Medicine, Laboratory Building, Haukeland University Hospital, Bergen, Norway

    Stephanie Le Hellard

  115. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Robert Levitan

  116. American School of Professional Psychology, Argosy University, Northern Virginia, Arlington, VA, USA

    Lisa Lilenfeld

  117. Department of Cancer Epidemiology and Prevention, M Skłodowska-Curie Cancer Center - Oncology Center, Warsaw, Poland

    Jolanta Lissowska

  118. BESE Division, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia

    Pierre Magistretti

  119. Department of Psychiatry, University of Lausanne-University Hospital of Lausanne (UNIL-CHUV), Lausanne, Switzerland

    Pierre Magistretti

  120. Department of Psychiatry, University of Campania ‘Luigi Vanvitelli’, Naples, Italy

    Mario Maj & Alessio Maria Monteleone

  121. Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

    Katrin Mannik

  122. Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada

    Christian Marshall

  123. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Manuel Mattheisen

  124. Department of Psychiatry, University College Cork, Cork, Ireland

    Sara McDevitt

  125. Eist Linn Adolescent Unit, Bessborough, Health Service Executive South, Cork, Ireland

    Sara McDevitt

  126. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    Andres Metspalu

  127. Molecular Epidemiology Section (Department of Medical Statistics), Leiden University Medical Centre, Leiden, the Netherlands

    Ingrid Meulenbelt & P. Eline Slagboom

  128. Department of Psychiatry, Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Nadia Micali

  129. Division of Child and Adolescent Psychiatry, Geneva University Hospital, Geneva, Switzerland

    Nadia Micali

  130. Department of Psychiatry and Behavioral Science, University of North Dakota School of Medicine and Health Sciences, Fargo, ND, USA

    James Mitchell

  131. National Center for PTSD, VA Boston Healthcare System, Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA

    Karen Mitchell

  132. Department of Medicine, Surgery and Dentistry ‘Scuola Medica Salernitana’, University of Salerno, Salerno, Italy

    Palmiero Monteleone

  133. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

    Grant Montgomery

  134. Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy

    Benedetta Nacmias, Valdo Ricca & Sandro Sorbi

  135. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA

    Roel Ophoff

  136. Kartini Clinic, Portland, OR, USA

    Julie O’Toole

  137. Center for Human Genome Research at the Massachusetts General Hospital, Boston, MA, USA

    Aarno Palotie & Aarno Palotie

  138. Biostatistics and Computational Biology Unit, University of Otago, Christchurch, New Zealand

    John Pearson

  139. Saint Joan de Déu Research Institute, Saint Joan de Déu Barcelona Children’s Hospital, Barcelona, Spain

    Raquel Rabionet

  140. Institute of Biomedicine (IBUB), University of Barcelona, Barcelona, Spain

    Raquel Rabionet

  141. Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain

    Raquel Rabionet

  142. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Ted Reichborn-Kjennerud

  143. Department of Health Science, University of Florence, Florence, Italy

    Valdo Ricca

  144. Department of Biometry, University of Helsinki, Helsinki, Finland

    Samuli Ripatti

  145. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

    Stephan Ripke

  146. Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA

    Stephan Ripke

  147. Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany

    Stephan Ripke

  148. Eating Disorders Research and Treatment Center, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany

    Franziska Ritschel

  149. Department of Psychiatry, Neurobiology, Pharmacology, and Biotechnologies, University of Pisa, Pisa, Italy

    Alessandro Rotondo

  150. Department of Psychiatry, Poznań University of Medical Sciences, Poznań, Poland

    Filip Rybakowski & Marta Tyszkiewicz-Nwafor

  151. Department of Neurosciences, Padua Neuroscience Center, University of Padova, Padua, Italy

    Paolo Santonastaso

  152. Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, Jena, Germany

    André Scherag

  153. Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada

    Stephen Scherer

  154. J. Craig Venter Institute (JCVI), La Jolla, CA, USA

    Nicholas Schork

  155. Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria

    Alexandra Schosser

  156. Department of Pediatrics and Center of Applied Genomics, First Faculty of Medicine, Charles University, Prague, Czech Republic

    Lenka Slachtova

  157. Center for Eating Disorders Ursula, Rivierduinen, Leiden, the Netherlands

    Margarita Slof-Op ‘t Landt & Eric van Furth

  158. Department of Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands

    Margarita Slof-Op ‘t Landt & Eric van Furth

  159. Department of Child and Adolescent Psychiatry, Poznań University of Medical Sciences, Poznań, Poland

    Agnieszka Slopien

  160. IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy

    Sandro Sorbi

  161. Department of Psychiatry and Biobehavioral Science, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA

    Michael Strober

  162. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Michael Strober

  163. Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Garret Stuber

  164. Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland

    Beata Świątkowska

  165. Department of Psychiatry, University of Naples SUN, Naples, Italy

    Alfonso Tortorella

  166. Department of Psychiatry, University of Perugia, Perugia, Italy

    Alfonso Tortorella

  167. Brain Sciences Department, Stremble Ventures, Limassol, Cyprus

    Federica Tozzi

  168. Adolescent Health Unit, Second Department of Pediatrics, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece

    Artemis Tsitsika

  169. Pediatric Intensive Care Unit, ‘P. & A. Kyriakou’ Children’s Hospital, University of Athens, Athens, Greece

    Konstantinos Tziouvas

  170. Faculty of Social and Behavioral Sciences, Utrecht University, Utrecht, the Netherlands

    Annemarie van Elburg

  171. School of Psychology, Flinders University, Adelaide, South Australia, Australia

    Tracey Wade

  172. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Thomas Werge

  173. Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    D. Blake Woodside

  174. Toronto General Hospital, Toronto, Ontario, Canada

    D. Blake Woodside

  175. Institute of Translational Genomics, Helmholtz Zentrum München, Neuherberg, Germany

    Eleftheria Zeggini

  176. Department of Internal Medicine VI, Psychosomatic Medicine and Psychotherapy, University Medical Hospital Tübingen, Tübingen, Germany

    Stephan Zipfel

  177. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Verneri Anttila, Ester Cuenca-Leon, Padhraig Gormley, Mitja Kurki & Benjamin M. Neale

  178. Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland

    Ville Artto & Mikko Kallela

  179. Karolinska Institutet, Stockholm, Sweden

    Andrea Carmine Belin

  180. Leiden University Medical Centre, Leiden, the Netherlands

    Irene de Boer, Michel Ferrari, Rune R. Frants, Arn van den Maagdenberg & Gisela Terwindt

  181. VU University, Amsterdam, the Netherlands

    Dorret I. Boomsma, Lannie Ligthart & Danielle Posthuma

  182. Oslo University Hospital and University of Oslo, Oslo, Norway

    Sigrid Børte, Linda Pedersen, Bendik S. Winsvold & John Anker Zwart

  183. Harvard Medical School, Cambridge, MA, USA

    Daniel I. Chasman

  184. Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK

    Lynn Cherkas & Massimo Mangino

  185. Danish Headache Center, Copenhagen University Hospital, Copenhagen, Denmark

    Anne Francke Christensen

  186. University of Barcelona, Barcelona, Spain

    Bru Cormand & Celia Sintas

  187. Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    George Davey-Smith & George McMahon

  188. Institute for Stroke and Dementia Research, Munich, Germany

    Martin Dichgans & Rainer Malik

  189. Erasmus University Medical Centre, Rotterdam, the Netherlands

    Cornelia van Duijn & M. Arfan Ikram

  190. Danish Headache Center, Department of Neurology, Rigshospitalet, Glostrup, Denmark

    Ann Louise Esserlind & Jes Olesen

  191. University of Tübingen, Tübingen, Germany

    Tobias Freilinger

  192. 23&Me Inc., Mountain View, CA, USA

    Nick Furlotte, Nadia Litterman & Carrie Northover

  193. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia

    Lyn Griffiths, Dale R. Nyholt & Huiying Zhao

  194. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland

    Eija Hamalainen, Risto Kajanne & Priit Palta

  195. Folkhälsan Institute of Genetics, Helsinki, Finland

    Marjo Hiekkala, Mari Kaunisto & Maija Wessman

  196. Decode genetics Inc., Reykjavik, Iceland

    Andres Ingason, Kari Stefansson, Hreinn Stefansson & Stacy Steinberg

  197. University of Oulu, Biocenter Oulu, Finland

    Marjo-Riitta Järvelin

  198. University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Christian Kubisch & Davor Lessel

  199. Harvard Medical School, Boston, MA, USA

    Tobias Kurth & Markus Schürks

  200. National Institute on Aging, Bethesda, MD, USA

    Lenore Launer

  201. School of Medicine, University of Tampere, Tampere, Finland

    Terho Lehtimaki

  202. Vall d’Hebron Research Institute, Barcelona, Spain

    Alfons Macaya & Marta Vila-Pueyo

  203. Max Planck Institute of Psychiatry, Munich, Germany

    Bertram Muller-Myhsok

  204. Headache Research Group, Universitat Autònoma de Barcelona, Barcelona, Spain

    Patricia Pozo-Rosich

  205. Sutter Health, Sacramento, CA, USA

    Alice Pressman

  206. Department of Medicine, University of Turku, Turku, Finland

    Olli Raitakari

  207. Population Health Research Institute, St George’s University of London, London, UK

    David Strachan

  208. 23andMe, Inc., Mountain View, CA, USA

    Michelle Agee, Babak Alipanahi, Adam Auton, Robert Bell, Katarzyna Bryc, Sarah Elson, Pierre Fontanillas, Nicholas Furlotte, Karl Heilbron, David Hinds, Karen Huber, Aaron Kleinman, Nadia Litterman, Jennifer McCreight, Matthew McIntyre, Joanna Mountain, Elizabeth Noblin, Carrie Northover, Steven Pitts, J. Sathirapongsasuti, Olga Sazonova, Janie Shelton, Suyash Shringarpure, Chao Tian, Joyce Tung, Vladimir Vacic & Catherine Wilson

Authors
  1. Julien Bryois
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathan G. Skene
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas Folkmann Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lisette J. A. Kogelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hunna J. Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zijing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leo Brueggeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gerome Breen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cynthia M. Bulik
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ernest Arenas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jens Hjerling-Leffler
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Patrick F. Sullivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Eating Disorders Working Group of the Psychiatric Genomics Consortium

  • Roger Adan
  • , Lars Alfredsson
  • , Tetsuya Ando
  • , Ole Andreassen
  • , Jessica Baker
  • , Andrew Bergen
  • , Wade Berrettini
  • , Andreas Birgegård
  • , Joseph Boden
  • , Ilka Boehm
  • , Claudette Boni
  • , Vesna Boraska Perica
  • , Harry Brandt
  • , Gerome Breen
  • , Julien Bryois
  • , Katharina Buehren
  • , Cynthia Bulik
  • , Roland Burghardt
  • , Matteo Cassina
  • , Sven Cichon
  • , Maurizio Clementi
  • , Jonathan Coleman
  • , Roger Cone
  • , Philippe Courtet
  • , Steven Crawford
  • , Scott Crow
  • , James Crowley
  • , Unna Danner
  • , Oliver Davis
  • , Martina de Zwaan
  • , George Dedoussis
  • , Daniela Degortes
  • , Janiece DeSocio
  • , Danielle Dick
  • , Dimitris Dikeos
  • , Christian Dina
  • , Monika Dmitrzak-Weglarz
  • , Elisa Docampo Martinez
  • , Laramie Duncan
  • , Karin Egberts
  • , Stefan Ehrlich
  • , Geòrgia Escaramís
  • , Tõnu Esko
  • , Xavier Estivill
  • , Anne Farmer
  • , Angela Favaro
  • , Fernando Fernández-Aranda
  • , Manfred Fichter
  • , Krista Fischer
  • , Manuel Föcker
  • , Lenka Foretova
  • , Andreas Forstner
  • , Monica Forzan
  • , Christopher Franklin
  • , Steven Gallinger
  • , Héléna Gaspar
  • , Ina Giegling
  • , Johanna Giuranna
  • , Paola Giusti-Rodríquez
  • , Fragiskos Gonidakis
  • , Scott Gordon
  • , Philip Gorwood
  • , Monica Gratacos Mayora
  • , Jakob Grove
  • , Sébastien Guillaume
  • , Yiran Guo
  • , Hakon Hakonarson
  • , Katherine Halmi
  • , Ken Hanscombe
  • , Konstantinos Hatzikotoulas
  • , Joanna Hauser
  • , Johannes Hebebrand
  • , Sietske Helder
  • , Anjali Henders
  • , Stefan Herms
  • , Beate Herpertz-Dahlmann
  • , Wolfgang Herzog
  • , Anke Hinney
  • , L. John Horwood
  • , Christopher Hübel
  • , Laura Huckins
  • , James Hudson
  • , Hartmut Imgart
  • , Hidetoshi Inoko
  • , Vladimir Janout
  • , Susana Jiménez-Murcia
  • , Craig Johnson
  • , Jennifer Jordan
  • , Antonio Julià
  • , Anders Juréus
  • , Gursharan Kalsi
  • , Deborah Kaminská
  • , Allan Kaplan
  • , Jaakko Kaprio
  • , Leila Karhunen
  • , Andreas Karwautz
  • , Martien Kas
  • , Walter Kaye
  • , James Kennedy
  • , Martin Kennedy
  • , Anna Keski-Rahkonen
  • , Kirsty Kiezebrink
  • , Youl-Ri Kim
  • , Katherine Kirk
  • , Lars Klareskog
  • , Kelly Klump
  • , Gun Peggy Knudsen
  • , Maria La Via
  • , Mikael Landén
  • , Janne Larsen
  • , Stephanie Le Hellard
  • , Virpi Leppä
  • , Robert Levitan
  • , Dong Li
  • , Paul Lichtenstein
  • , Lisa Lilenfeld
  • , Bochao Danae Lin
  • , Jolanta Lissowska
  • , Jurjen Luykx
  • , Pierre Magistretti
  • , Mario Maj
  • , Katrin Mannik
  • , Sara Marsal
  • , Christian Marshall
  • , Nicholas Martin
  • , Manuel Mattheisen
  • , Morten Mattingsdal
  • , Sara McDevitt
  • , Peter McGuffin
  • , Sarah Medland
  • , Andres Metspalu
  • , Ingrid Meulenbelt
  • , Nadia Micali
  • , James Mitchell
  • , Karen Mitchell
  • , Palmiero Monteleone
  • , Alessio Maria Monteleone
  • , Grant Montgomery
  • , Preben Bo Mortensen
  • , Melissa Munn-Chernoff
  • , Benedetta Nacmias
  • , Marie Navratilova
  • , Claes Norring
  • , Ioanna Ntalla
  • , Catherine Olsen
  • , Roel Ophoff
  • , Julie O’Toole
  • , Leonid Padyukov
  • , Aarno Palotie
  • , Jacques Pantel
  • , Hana Papezova
  • , Richard Parker
  • , John Pearson
  • , Nancy Pedersen
  • , Liselotte Petersen
  • , Dalila Pinto
  • , Kirstin Purves
  • , Raquel Rabionet
  • , Anu Raevuori
  • , Nicolas Ramoz
  • , Ted Reichborn-Kjennerud
  • , Valdo Ricca
  • , Samuli Ripatti
  • , Stephan Ripke
  • , Franziska Ritschel
  • , Marion Roberts
  • , Alessandro Rotondo
  • , Dan Rujescu
  • , Filip Rybakowski
  • , Paolo Santonastaso
  • , André Scherag
  • , Stephen Scherer
  • , Ulrike Schmidt
  • , Nicholas Schork
  • , Alexandra Schosser
  • , Jochen Seitz
  • , Lenka Slachtova
  • , P. Eline Slagboom
  • , Margarita Slof-Op ‘t Landt
  • , Agnieszka Slopien
  • , Sandro Sorbi
  • , Michael Strober
  • , Garret Stuber
  • , Patrick Sullivan
  • , Beata Świątkowska
  • , Jin Szatkiewicz
  • , Ioanna Tachmazidou
  • , Elena Tenconi
  • , Laura Thornton
  • , Alfonso Tortorella
  • , Federica Tozzi
  • , Janet Treasure
  • , Artemis Tsitsika
  • , Marta Tyszkiewicz-Nwafor
  • , Konstantinos Tziouvas
  • , Annemarie van Elburg
  • , Eric van Furth
  • , Tracey Wade
  • , Gudrun Wagner
  • , Esther Walton
  • , Hunna Watson
  • , Thomas Werge
  • , David Whiteman
  • , Elisabeth Widen
  • , D. Blake Woodside
  • , Shuyang Yao
  • , Zeynep Yilmaz
  • , Eleftheria Zeggini
  • , Stephanie Zerwas
  •  & Stephan Zipfel

International Headache Genetics Consortium

  • Verneri Anttila
  • , Ville Artto
  • , Andrea Carmine Belin
  • , Irene de Boer
  • , Dorret I. Boomsma
  • , Sigrid Børte
  • , Daniel I. Chasman
  • , Lynn Cherkas
  • , Anne Francke Christensen
  • , Bru Cormand
  • , Ester Cuenca-Leon
  • , George Davey-Smith
  • , Martin Dichgans
  • , Cornelia van Duijn
  • , Tonu Esko
  • , Ann Louise Esserlind
  • , Michel Ferrari
  • , Rune R. Frants
  • , Tobias Freilinger
  • , Nick Furlotte
  • , Padhraig Gormley
  • , Lyn Griffiths
  • , Eija Hamalainen
  • , Thomas Folkmann Hansen
  • , Marjo Hiekkala
  • , M. Arfan Ikram
  • , Andres Ingason
  • , Marjo-Riitta Järvelin
  • , Risto Kajanne
  • , Mikko Kallela
  • , Jaakko Kaprio
  • , Mari Kaunisto
  • , Lisette J. A. Kogelman
  • , Christian Kubisch
  • , Mitja Kurki
  • , Tobias Kurth
  • , Lenore Launer
  • , Terho Lehtimaki
  • , Davor Lessel
  • , Lannie Ligthart
  • , Nadia Litterman
  • , Arn van den Maagdenberg
  • , Alfons Macaya
  • , Rainer Malik
  • , Massimo Mangino
  • , George McMahon
  • , Bertram Muller-Myhsok
  • , Benjamin M. Neale
  • , Carrie Northover
  • , Dale R. Nyholt
  • , Jes Olesen
  • , Aarno Palotie
  • , Priit Palta
  • , Linda Pedersen
  • , Nancy Pedersen
  • , Danielle Posthuma
  • , Patricia Pozo-Rosich
  • , Alice Pressman
  • , Olli Raitakari
  • , Markus Schürks
  • , Celia Sintas
  • , Kari Stefansson
  • , Hreinn Stefansson
  • , Stacy Steinberg
  • , David Strachan
  • , Gisela Terwindt
  • , Marta Vila-Pueyo
  • , Maija Wessman
  • , Bendik S. Winsvold
  • , Huiying Zhao
  •  & John Anker Zwart

23andMe Research Team

  • Michelle Agee
  • , Babak Alipanahi
  • , Adam Auton
  • , Robert Bell
  • , Katarzyna Bryc
  • , Sarah Elson
  • , Pierre Fontanillas
  • , Nicholas Furlotte
  • , Karl Heilbron
  • , David Hinds
  • , Karen Huber
  • , Aaron Kleinman
  • , Nadia Litterman
  • , Jennifer McCreight
  • , Matthew McIntyre
  • , Joanna Mountain
  • , Elizabeth Noblin
  • , Carrie Northover
  • , Steven Pitts
  • , J. Sathirapongsasuti
  • , Olga Sazonova
  • , Janie Shelton
  • , Suyash Shringarpure
  • , Chao Tian
  • , Joyce Tung
  • , Vladimir Vacic
  •  & Catherine Wilson

Contributions

J.B., N.G.S., J.H.-L. and P.F.S. designed the study, and wrote and reviewed the manuscript; J.B. performed the analyses pertaining to Figs. 1–4, Extended Data Figs. 1–10, Supplementary Figs. 1–5 and 7–20, and Supplementary Tables 1–9 and 12–17; N.G.S performed the analyses pertaining to Fig. 5, Supplementary Fig. 6 and Supplementary Tables 10 and 11; T.F.H., L.J.A.K. and the I.H.G.C. provided the migraine GWAS summary statistics; H.J.W., the E.D.W.G.P.G.C., G.B. and C.M.B. performed the anorexia GWAS; Z.L. contributed to the revision of the manuscript, the 23andMe R.T. provided GWAS summary statistics for Parkinson’s disease in the 23andMe cohort. L.B. contributed to the post-mortem differential expression analysis (Fig. 5); E.A. provided expert knowledge on Parkinson’s disease and reviewed the manuscript.

Corresponding authors

Correspondence to Jens Hjerling-Leffler or Patrick F. Sullivan.

Ethics declarations

Competing interests

P.F.S. reports the following potentially competing financial interests: current—Lundbeck (advisory committee, grant recipient); past three years—Pfizer (scientific advisory board), Element Genomics (consultation fee) and Roche (speaker reimbursement). C.M.B. reports: Shire (grant recipient, Scientific Advisory Board member); Pearson and Walker (author, royalty recipient).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Enrichment of immune genes in GTEx tissues.

Enrichment pvalues of genes belonging to the GO term ‘Immune System Process’ in the 10% most specific genes in each tissue. The one-sided pvalues were computed using linear regression, testing whether the average specificity metric of the gene set was higher than 0 (z-scaled specificity metrics per tissue). The GO term was selected because it is the most associated with inflammatory bowel disease using MAGMA.

Extended Data Fig. 2 Associations of brain related traits with cell types from the entire mouse nervous system.

Associations of the top 15 most associated cell types are shown. The mean strength of association (-log10P) of MAGMA and LDSC is shown and the bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold: 5% false discovery rate).

Extended Data Fig. 3 Correlation in cell type associations across traits.

The Spearman rank correlations between the cell types associations across traits (-log10P) are shown. SCZ (schizophrenia), EDU (educational attainment), INT (intelligence), BMI (body mass index), BIP (bipolar disorder), NEU (neuroticism), PAR (Parkinson’s disease), MDD (Major depressive disorder), MEN (age at menarche), ICV (intracranial volume), ASD (autism spectrum disorder), STR (stroke), AN (anorexia nervosa), MIG (migraine), ALS (amyotrophic lateral sclerosis), ADHD (attention deficit hyperactivity disorder), ALZ (Alzheimer’s disease), HIP (hippocampal volume).

Extended Data Fig. 4 Associations of brain related traits with neurons from the central nervous system.

Associations of the 15 most associated neurons from the central nervous system (CNS) are shown. The specificity metrics were computed only using neurons from the CNS. The mean strength of association (-log10P) of MAGMA and LDSC is shown and the bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold: 5% false discovery rate).

Extended Data Fig. 5 Associations of cell types with schizophrenia/cognitive traits conditioning on gene-level genetic association of cognitive traits/schizophrenia.

MAGMA association strength for each cell type before and after conditioning on gene-level genetic association for another trait. The black bar represents the significance threshold (5% false discovery rate). SCZ (schizophrenia), INT (intelligence), EDU (educational attainment).

Extended Data Fig. 6 Replication of cell type—trait associations in 88 cell types from 9 different brain regions.

The mean strength of association (-log10P) of MAGMA and LDSC is shown for the 15 top cell types for each trait. The bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold: 5% false discovery rate).

Extended Data Fig. 7 Correlation in cell type associations across traits in a replication data set (88 cell types, 9 brain regions).

Spearman rank correlations for cell types associations (-log10P) across traits are shown. SCZ (schizophrenia), EDU (educational attainment), INT (intelligence), BMI (body mass index), BIP (bipolar disorder), NEU (neuroticism), PAR (Parkinson’s disease), MDD (Major depressive disorder), MEN (age at menarche), ICV (intracranial volume), ASD (autism spectrum disorder), STR (stroke), AN (anorexia nervosa), MIG (migraine), ALS (amyotrophic lateral sclerosis), ADHD (attention deficit hyperactivity disorder), ALZ (Alzheimer’s disease), HIP (hippocampal volume).

Extended Data Fig. 8 Associations of brain related traits with neurons from 9 different brain regions.

Trait—neuron association are shown for neurons of the 9 different brain regions. The specificity metrics were computed only using neurons. The mean strength of association (-log10P) of MAGMA and LDSC is shown and the bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold: 5% false discovery rate).

Extended Data Fig. 9 Top associated cell types with brain related traits among 24 cell types from 5 different brain regions.

The mean strength of association (-log10P) of MAGMA and LDSC is shown for the 15 top cell types for each trait. The bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold: 5% false discovery rate).

Extended Data Fig. 10 Top associated neurons with brain related traits among 16 neurons from 5 different brain regions.

The specificity metrics were computed only using neurons. The mean strength of association (-log10P) of MAGMA and LDSC is shown for the top 15 cell types for each trait. The bar color indicates whether the cell type is significantly associated with both methods, one method or none (significance threshold= 5% false discovery rate).

Supplementary information

Supplementary Information

Supplementary Figs. 1–20 and Note

Reporting Summary

Supplementary Tables

Supplementary Tables 1–17

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bryois, J., Skene, N.G., Hansen, T.F. et al. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease. Nat Genet 52, 482–493 (2020). https://doi.org/10.1038/s41588-020-0610-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41588-020-0610-9

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research