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Association analysis identifies new risk loci for congenital heart disease in Chinese populations
Genome-wide association studies in Chinese and Europeans have identified multiple loci associated with congenital heart disease. Here the authors use existing GWAS data to conduct an extended three-stage analysis in Han Chinese and identify four novel loci linked to disease risk in this population.
- Yuan Lin
- , Xuejiang Guo
- & Zhibin Hu
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| Open AccessGenome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations
Polycystic Ovary Sydrome is a highly heritable, complex reproductive disorder with unknown underlying genetic factors. Here Hayes and Urbanek et al. identify three loci in European women strongly associated with neuroendocrine changes and disease susceptibility.
- M. Geoffrey Hayes
- , Margrit Urbanek
- & Andrea Dunaif
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| Open AccessCommon and rare variants associated with kidney stones and biochemical traits
Kidney stone formation is influenced by genetic factors and recurrent stone formation places a significant burden on health care systems. Here Oddsson et al.perform a large-scale genome-wide association study and uncover new genetic variants associated with kidney stone susceptibility and associated biochemical traits.
- Asmundur Oddsson
- , Patrick Sulem
- & Kari Stefansson
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| Open AccessGenetic, molecular and physiological basis of variation in Drosophila gut immunocompetence
Animals rely on a multitude of resistance and tolerance mechanisms to resist harmful gut microbes. Here, the authors explore the genetic, molecular and physiological basis underlying the remarkable phenotypic variation in resistance to enteric bacterial infection inDrosophila melanogaster.
- Maroun S. Bou Sleiman
- , Dani Osman
- & Bart Deplancke
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Genome-wide association study identifies variants at 16p13 associated with survival in multiple myeloma patients
Multiple myeloma is an incurable blood cancer with family history being a strong contributing risk factor. Here Ziv et al.perform a genome-wide association study for genetic variation associated with myeloma survival, identifying FOPNL variants associated with worse clinical outcomes.
- Elad Ziv
- , Eric Dean
- & Celine Vachon
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| Open AccessThree missense variants of metabolic syndrome-related genes are associated with alpha-1 antitrypsin levels
Alpha-1 antitrypsin deficiency is a common genetic disorder in Europeans. Here Setohet al. perform a genome-wide association study of AAT serum levels in a Japanese population and find three missense variants in the metabolism genes ALDH2, HNF1A and GCKR.
- Kazuya Setoh
- , Chikashi Terao
- & Fumihiko Matsuda
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| Open AccessGenome-wide burden of deleterious coding variants increased in schizophrenia
Schizophrenia is a complex disorder with high heritability but poorly understood genetics. Here Olde Loohuis et al.compare schizophrenia patients to unaffected individuals and identify an increased individual burden of rare deleterious mutations in patients.
- Loes M. Olde Loohuis
- , Jacob A. S. Vorstman
- & Roel A. Ophoff
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| Open AccessGenetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study
Graves’ disease is the leading cause of hyperthyroidism but treatment options can cause life-threatening complications. Chen et al. conduct two-stage direct HLA genotyping and genome-wide association studies to identify HLA-B*38:02 and HLA-DRB1*08:03 as major pharmacogenetic determinants.
- Pei-Lung Chen
- , Shyang-Rong Shih
- & Tien-Chun Chang
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Genome-wide association study of colorectal cancer identifies six new susceptibility loci
Previous studies have shown that both rare pathogenic mutations and common genetic variants contribute to the familial risk of developing colorectal cancer. Here, the authors carry out a two-stage genome-wide association study and identify six new loci associated with colorectal cancer.
- Fredrick R. Schumacher
- , Stephanie L. Schmit
- & Ulrike Peters
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A random forest approach to capture genetic effects in the presence of population structure
The discovery and mapping of causal variants in genome-wide association studies requires taking into consideration a range of confounding factors that can impact the results of the analysis. Here Stephanet al. propose a mixed random forest that captures nonlinear associations while accounting for population structure simultaneously.
- Johannes Stephan
- , Oliver Stegle
- & Andreas Beyer
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| Open AccessInherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children
Genome-wide association studies indicate a strong genetic susceptibility to acute lymphoblastic leukaemia in children, though the effect on protein-coding genes is not fully understood. Here Xu and Zhang et al. identify a missense variant in CDKN2Awhich reduces tumour suppression.
- Heng Xu
- , Hui Zhang
- & Jun J. Yang
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| Open AccessGenome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy
Corticobasal degeneration is a rare neurodegenerative disorder that can only be definitively diagnosed by autopsy. Here, Kouri et al. conduct a genome-wide-association study and identify two genetic susceptibility loci 17q21 (MAPT) and 3p12 (MOBP), and a novel susceptibility locus at 8p12.
- Naomi Kouri
- , Owen A. Ross
- & Dennis W. Dickson
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Genome-wide association study identifies novel genetic variants contributing to variation in blood metabolite levels
Metabolites are important indicators of the physiological state of the body and potential biomarkers for disease. Here, Draisma et al. use a genome-wide association study to identify novel single-nucleotide polymorphisms associated with blood metabolite levels in genes of pharmaceutical importance.
- Harmen H. M. Draisma
- , René Pool
- & Dorret I. Boomsma
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Analysis of deletion breakpoints from 1,092 humans reveals details of mutation mechanisms
Structural variation is a major source of complexity in the human genome. Here Abyzov et al.present the identification, classification and analysis of a large database of variants giving an insight into mechanisms generating them.
- Alexej Abyzov
- , Shantao Li
- & Mark B. Gerstein
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| Open AccessIdentification of new susceptibility loci for IgA nephropathy in Han Chinese
IgA nephropathy is a major cause of end-stage renal disease in China, occurring at a high frequency in Asian populations. Here Li and colleagues conduct a four-stage genome-wide association study in a Chinese population, identifying novel loci and variants associated with disease risk.
- Ming Li
- , Jia-Nee Foo
- & Jian-Jun Liu
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| Open AccessA Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease
In order to effectively design interventions, it is useful to understand the complex interplay between multiple syndromes. Here, Ahmad et al. use genome-wide association study data and Mendelian randomisation to examine the influence of Type 2 diabetes and fasting glucose levels on coronary heart disease.
- Omar S. Ahmad
- , John A. Morris
- & J. Brent Richards
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| Open AccessVariants in ELL2 influencing immunoglobulin levels associate with multiple myeloma
Multiple myeloma is an incurable and fatal disease characterized by uninhibited growth of plasma cells in the bone marrow. Here, Swaminathan et al. conduct a genome-wide association study and identify a novel risk locus at ELL2, which encodes a key component of the super-elongation complex.
- Bhairavi Swaminathan
- , Guðmar Thorleifsson
- & Björn Nilsson
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| Open AccessAllele-specific analysis of DNA replication origins in mammalian cells
DNA sequences contribute to the location and timing of replication origin firings. Here by allele-specific analysis, the authors show that replication asynchrony is associated with small cumulative variations in the initiation efficiency of origins, rather than with the activation of dormant origins.
- Boris Bartholdy
- , Rituparna Mukhopadhyay
- & Eric E. Bouhassira
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| Open AccessGenome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese
Raised serum urate levels are a risk factor for gout, a common form of inflammatory arthritis. Here Li et al.conduct a multistage genome-wide association study in a Han Chinese population and identify three novel loci likely associated with the progression from hyperuricemia to gout.
- Changgui Li
- , Zhiqiang Li
- & Yongyong Shi
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eQTL mapping identifies insertion- and deletion-specific eQTLs in multiple tissues
Expression quantitative trait loci (eQTLs) may provide insight into the functional mechanisms underlying disease risk variants. Here the authors characterize INDEL-specific eQTLs in several tissues and show that these can have both tissue-specific and tissue-consistent effects.
- Jinyan Huang
- , Jun Chen
- & Liming Liang
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Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci
About 2% of the population are affected by psoriasis, a chronic skin disease with complex genetics. Here Tsoi et al.conduct a meta-analysis of several genome-wide association studies and identify five novel loci, helping to further our understanding of the biology behind this condition.
- Lam C. Tsoi
- , Sarah L. Spain
- & James T. Elder
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Association of CLEC16A with human common variable immunodeficiency disorder and role in murine B cells
Common variable immunodeficiency disorder (CVID) is a primary immunodeficiency with autoimmune comorbidity. Here, Li et al. show shared genetic susceptibility with autoimmune diseases, identifying the first non HLA risk locus at CLEC16Ain the largest CVID genetic study to date.
- Jin Li
- , Silje F. Jørgensen
- & Eva Ellinghaus
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| Open AccessWhole-exome SNP array identifies 15 new susceptibility loci for psoriasis
Psoriasis is a chronic inflammatory disease affecting up to 3% of the population. Here, Zuo et al.perform exome array analysis, identify single-nucleotide polymorphisms at 15 new loci, implicating several biological pathways in psoriasis risk and disease heritability.
- Xianbo Zuo
- , Liangdan Sun
- & Xuejun Zhang
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| Open AccessGenetic variation at MECOM, TERT, JAK2 and HBS1L-MYB predisposes to myeloproliferative neoplasms
Somatic mutations drive the clonal proliferation of myeloproliferative neoplasms. Here the authors conduct a genome-wide association study and identify germline variation at multiple loci associated with the development and disease phenotype of these cancers.
- William Tapper
- , Amy V. Jones
- & Nicholas C.P. Cross
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| Open AccessA PAX1 enhancer locus is associated with susceptibility to idiopathic scoliosis in females
Girls are tenfold more likely than boys to require surgical treatment for idiopathic scoliosis, a common paediatric skeletal disorder. Here, Sharma et al. identify the first sexually dimorphic idiopathic scoliosis risk locus, and demonstrate that it may play a role in the regulation of spinal cells.
- Swarkar Sharma
- , Douglas Londono
- & Carol A. Wise
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Genome-wide association study identifies a new susceptibility locus for cleft lip with or without a cleft palate
Cleft lip is one of the most common congenital birth defects with substantial impairments to quality of life. Here, Sun et al. identify a new locus associated with cleft lip in diverse Chinese populations.
- Yimin Sun
- , Yongqing Huang
- & Yinxue Yang
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Gut microbiome development along the colorectal adenoma–carcinoma sequence
The gut microbiota is involved in the development of colorectal cancer. Here, the authors analyse the faecal microbiomes of healthy subjects and of patients with colorectal cancer or benign adenoma, revealing microbial genes, strains and functions enriched in each group.
- Qiang Feng
- , Suisha Liang
- & Jun Wang
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| Open AccessGenome of the Netherlands population-specific imputations identify an ABCA6 variant associated with cholesterol levels
Frequencies of rare variants fluctuate over populations, hampering gene discovery. Here the authors use a population-specific reference panel, the Genome of the Netherlands, to discover four novel loci involved in lipid metabolism, including an exonic variant in ABCA6.
- Elisabeth M. van Leeuwen
- , Lennart C. Karssen
- & Cornelia M. van Duijn
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Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children
Food allergy is a growing clinical and public health burden. Here, the authors carry out a genome-wide association study in samples with well-defined allergies to a variety of foods, and identify the 6p21.32 region that significantly increases risk of developing peanut allergy.
- Xiumei Hong
- , Ke Hao
- & Xiaobin Wang
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Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster
The gut microbiota affects animal nutrition, but it is unclear whether this effect depends on host genetic makeup. This study shows that host genotype modifies the gut microbiota’s impact on host nutrition, and identifies genetic determinants of this variation in the fruit fly.
- Adam J. Dobson
- , John M. Chaston
- & Angela E. Douglas
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| Open AccessNew loci and coding variants confer risk for age-related macular degeneration in East Asians
Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Here, the authors carry out a two-stage genome-wide association study for AMD and identify three new AMD risk loci, highlighting the shared and distinct genetic basis of the disease in East Asians and Europeans.
- Ching-Yu Cheng
- , Kenji Yamashiro
- & Chiea Chuen Khor
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Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus
Neurological disorders such as temporal lobe epilepsy (TLE) are known to be regulated by gene networks. In this study, the authors describe a genome-wide approach that uses samples of hippocampal tissue from patients with TLE, to identify the gene Sestrin 3 (SESN3) as a positive regulator of the disease.
- Michael R. Johnson
- , Jacques Behmoaras
- & Enrico Petretto
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Biological interpretation of genome-wide association studies using predicted gene functions
Identifying which genes and pathways explain genetic associations is challenging. Here, the authors present DEPICT, a tool for gene prioritization, pathway analysis and tissue/cell-type enrichment analysis that can be used to generate testable hypotheses from genetic association studies.
- Tune H. Pers
- , Juha M. Karjalainen
- & Lude Franke
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| Open AccessA genome-wide association study of marginal zone lymphoma shows association to the HLA region
Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.
- Joseph Vijai
- , Zhaoming Wang
- & Alexandra Nieters
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Extrachromosomal driver mutations in glioblastoma and low-grade glioma
Human cancers are characterised by increased levels of genomic instability. Here, the authors show that a new class of mutation that occurs in glioblastoma, double minutes, may facilitate tumour drug resistance by acquiring gain-of-function extrachromosomal mutations, mediated by focal amplifications.
- Sergey Nikolaev
- , Federico Santoni
- & Stylianos E. Antonarakis
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GWAS identifies four novel eosinophilic esophagitis loci
Eosinophilic oesophagitis (EoE) is an allergic, inflammatory disorder of the oesophagus. Here the authors carry out a genome-wide association study in over 5,000 individuals and identify four genetic loci that affect the onset of EoE.
- Patrick M. A. Sleiman
- , Mei-Lun Wang
- & Hakon Hakonarson
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Genome-wide association study of Arabidopsis thaliana leaf microbial community
The effect of a host's genetic variation on the structure of its microbial community is poorly understood. Here, Horton et al. reveal associations between genetic variants in the plant model species Arabidopsis thalianaand the composition of the leaves' microbial communities.
- Matthew W. Horton
- , Natacha Bodenhausen
- & Joy Bergelson
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| Open AccessMeta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process
Glaucoma is the most common cause of irreversible blindness worldwide. Here, the authors carry out a large meta-analysis of genetic data from individuals of European and Asian ancestry and identify 10 new loci associated with vertical cup-disc ratio, a key factor in the clinical assessment of patients with glaucoma.
- Henriët. Springelkamp
- , René Höhn
- & Christopher J. Hammond
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Genome-wide association study identifies new susceptibility loci for epithelial ovarian cancer in Han Chinese women
Ovarian cancer is common among women and is the leading cause of death from gynaecological malignancies. Here the authors identify two previously unknown genetic variants that increase the risk of epithelial ovarian cancer in Han Chinese women.
- Kexin Chen
- , Hongxia Ma
- & Qingyi Wei
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Trans-ethnic genome-wide association study of colorectal cancer identifies a new susceptibility locus in VTI1A
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide and genetic susceptibility to the disease is poorly understood. Here, the authors combine data from Japanese, African American and European samples and identify a common variant in VTI1Athat increases CRC risk across all populations.
- Hansong Wang
- , Terrilea Burnett
- & Loïc Le Marchand
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| Open AccessThe correlation between reading and mathematics ability at age twelve has a substantial genetic component
Understanding the genetic basis of cognitive traits could aid the development of numeracy and literacy skills in children. Here the authors show that reading and mathematics have a large overlapping genetic component and suggest that a child's learning environment has a key role in creating differences between them.
- Oliver S. P. Davis
- , Gavin Band
- & Chris C. A. Spencer
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Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris
Acne vulgarisis a common, inflammatory skin disorder. Here the authors carry out a genome-wide association study and identify three genetic variants that associate with an increased risk of developing acne, which together suggest a mechanistic role for the TGFβ cell signalling pathway in acne development and progression.
- Alexander A. Navarini
- , Michael A. Simpson
- & Jonathan N. Barker
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| Open AccessMetabolome-based genome-wide association study of maize kernel leads to novel biochemical insights
Plants produce a variety of metabolites that have a critical role in growth and development. Here, the authors carry out a genome-wide association analysis of metabolites and metabolite features in maize and identify candidate genes involved in secondary metabolism, and a potential biomarker for the genetic improvement of the crop.
- Weiwei Wen
- , Dong Li
- & Jianbing Yan
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Genome-wide association study reveals two new risk loci for bipolar disorder
Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.
- Thomas W. Mühleisen
- , Markus Leber
- & Sven Cichon
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| Open AccessGenome-wide association study implicates NDST3 in schizophrenia and bipolar disorder
Schizophrenia and bipolar disorder are important psychiatric disorders with overlapping genetic components. Here, the authors identify and replicate a genome-wide significant risk locus for the two disorders, and suggest a role for NDST3in severe psychiatric disease.
- Todd Lencz
- , Saurav Guha
- & Ariel Darvasi
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| Open AccessIdentification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31
Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.
- Jennifer Permuth-Wey
- , Kate Lawrenson
- & Simon A. Gayther
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| Open AccessGenome-wide association mapping reveals a rich genetic architecture of complex traits in Oryza sativa
Understanding the genetics and physiology of domesticated species is important for crop improvement. By studying natural variation and the phenotypic traits of 413 diverse accessions of rice, Zhao et al. identify many common genetic variants that influence quantitative traits such as seed size and flowering time.
- Keyan Zhao
- , Chih-Wei Tung
- & Susan R. McCouch