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New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders


Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d−1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

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Fig. 1: Results of the discovery genome-wide association meta-analysis with alcohol consumption.
Fig. 2: Association of alcohol intake loci with other traits.
Fig. 3: Mediation effect of the grey-matter volume of bilateral putamen on the relationship between SNP rs13107325 and alcohol intake.
Fig. 4: Comparison of ZIP8 alcohol phenotypes in Drosophila.

Data availability

The UKB GWAS data can be assessed from the UKB data repository ( The genetic and phenotypic UKB data are available through application to the UKB ( Summary GWAS data can be assessed by request to the corresponding authors and are available at LDHub (


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H.G. was funded by the NIHR Imperial College Health Care NHS Trust and Imperial College London Biomedical Research Centre. I.K. was supported by the EU PhenoMeNal project (Horizon 2020, grant no. 654241) and the UK Dementia Research Institute, which is supported by the MRC, the Alzheimer’s Society and Alzheimer’s Research UK. S. Thériault was supported by the Canadian Institutes of Health Research and Université Laval (Quebec City, Canada). L.R. was supported by Forschungs- und Förder-Stiftung INOVA, Vaduz, Liechtenstein. D.C. holds a McMaster University Department of Medicine Mid-Career Research Award. M.B. is supported by NIH grant R01-DK062370. P.v.d.H. was supported by ICIN-NHI and Marie Skłodowska-Curie GF (call: H2020-MSCA-IF-2014; Project ID: 661395). C.H. was supported by a core MRC grant to the MRCHGU QTL in Health and Disease research programme. N.V. was supported by Marie Skłodowska-Curie GF (grant no. 661395) and ICIN-NHI. Q.L. is partially supported by the National Natural Sciences Foundation of China (No. 81873909), Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01) and ZJLab. P.E. acknowledges support from the NIHR Biomedical Research Centre at Imperial College Healthcare NHS Trust and Imperial College London, the NIHR Health Protection Research Unit in Health Impact of Environmental Hazards (HPRU-2012-10141), the Medical Research Council (MRC) and Public Health England (PHE) Centre for Environment and Health (MR/L01341X/1) and Health Data Research (HDR) UK. P.E. is supported by a UK Dementia Research Institute (DRI) professorship, UK DRI at Imperial College London, funded by the MRC, Alzheimer’s Society and Alzheimer’s Research UK. This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology; LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders; grant no. 695313), ERANID (Understanding the interplay between cultural, biological and subjective factors in drug use pathways; PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics; MR/N027558/1), the FP7 projects IMAGEMEND (grant no. 602450; IMAging GEnetics for MENtal Disorders) and MATRICS (grant no. 603016), the Innovative Medicine Initiative Project EU-AIMS (grant. no115300-2), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions; MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; and Forschungsnetz AERIAL 01EE1406A and 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2 and SFB 940/2), the Medical Research Foundation and Medical Research Council (MR/R00465X/1), the Human Brain Project (HBP SGA 2). Further support was provided by grants from ANR (project AF12-NEUR0008-01-WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1); and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information




Central analysis: E.E., H.G., C.C., G.N., P.B., A.R.B., R.P., H. Suzuki, F.K., A.M.Y., I.K., J.E., Q.L., N.D., D.L., I.T., J.D.B., P.M.M., A.R., S.D., G.S. and P.E. Writing of the manuscript: E.E., H.G., C.C., G.N., P.B., A.R.B., R.P., H. Suzuki, F.K., A.M.Y., I.K., D.L., I.T., J.D.B., P.M.M., A.R., S.D., G.S. and P.E. Association of MRI analysis: C.C., H. Suzuki, A.M.Y., A.I.B., J.D.B., P.M.M. and G.S. AlcGen and Charge+ contributors, by study: (ARIC): A.C.M., M.R.B., B.Y. and D.E.A. (CHS): B.M.P., R.N.L., T.M.B. and J.A.B. (FHS): D.L. and C.L. (GAPP/Swiss-AF/Beat-AF): S. Thériault, S.A., D.C., L.R. and M. Kühne. (GENOA): S.L.R.K., J.A.S., W.Z. and S.M.R., (GRAPHIC): N.J.S., C.P.N. and P.S.B., (GS): A.M.M., T.-K.C., C.H. and D.P., (HBCS): J.L., S. Tuominen, M.-M.P. and J.G.E. (HRS): D.R.W., S.L.R.K., J.D.F., W.Z. and J.A.S. (MESA): X.G., J.Y., A.W. and J.I.R. (METSIM): M.L., A.S., J. Vangipurapu and J.K. (FUSION): M.B., K.L.M., L.J.S. and A.U.J. (NESDA): B.W.J.H.P. and Y.M. (NFBC): M.-R.J., J. Veijola, M. Männikkö and J.A. (ORCADES): H.C. and P.K.J. (VIKING): J.F.W. and K.A.K. (Croatia-VIS): I.R. and O.P. (Croatia-KORCULA): C.H. (PREVEND): N.V. and P.v.d.H. (OZALC): N.G.M., J.B.W., P.A.L. and A.C.H. (SHIP): A.T., H.J.G., S.E.B. and G.H. (TRAILS-pop): A.J.O. and I.M.N. (TRAILS-CC): C.A.H. and H. Snieder. (TwinsUK): T.D.S. and M. Mangino. (YFS): L.-P.L., M. Kähönen, O.T.R. and T.L. All authors critically reviewed and approved the final version of the manuscript

Corresponding authors

Correspondence to Gunter Schumann or Paul Elliott.

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Competing interests

B.M.P. serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. B.W.J.H.P. has received research funding (unrelated to the work reported here) from Jansen Research and Boehringer Ingelheim. The other authors declare no competing interests.

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Evangelou, E., Gao, H., Chu, C. et al. New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders. Nat Hum Behav 3, 950–961 (2019).

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