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

Author
item EVANGELOU, EVANGELOS - Imperial College
item GAO, HE - Imperial College
item CHU, CONGYING - King'S College
item NRITSOS, GEORGIOS - University Of Ioannina
item BLAKELEY, PAUL - Imperial College
item BUTTS, ANDREW - University Of Utah
item PAZOKI, RAHA - Imperial College
item SUZUKI, HIDEAKI - Imperial College
item KOSKERIDIS, FOTIOS - University Of Ioannina
item YIORKAS, ANDRIANOS - Imperial College
item KARAMAN, IBRAHIM - Imperial College
item ELLIOTT, JOSHUA - Imperial College
item LUO, QIANG - Fudan University
item AESCHBACHER, STEFANIE - University Hospital Of Basel
item BARTZ, TRACI - University Of Washington
item BAUMEISTER, SEBASTIAN - University Of Greifswald
item BRAUND, PETER - University Of Leicester
item BROWN, MICHAEL - University Of Texas Health Science Center
item BRODY, JENNIFER - University Of Washington
item CLARKE, TONI - University Of Edinburgh
item DIMOU, NIKI - University Of Ioannina
item FAUL, JESSICA - University Of Michigan
item HOMUTH, GEORG - University Of Greifswald
item JACKSON, ANNE - University Of Michigan
item KENTISTOU, KATHERINE - University Of Edinburgh
item JOSHI, PETER - University Of Edinburgh
item LEMAITRE, ROZENN - University Of Washington
item LIND, PENELOPE - Qimr Berghofer Medical Research Institute
item LYYTIKAINEN, LEO - Tampere University Hospital
item MANGINO, MASSIMO - King'S College
item MILANESCHI, YURI - University Of Amsterdam
item NELSON, CHRISTOPHER - University Of Leicester
item NOLTE, ILJA - University Of Groningen
item PERALA, MIA - National Institute For Health And Welfare (HELSINKI)
item POLASEK, OZREN - University Of Split
item PORTEOUS, DAVID - University Of Edinburgh
item RATIFF, SCOTT - University Of Michigan
item SMITH, JENNIFER - University Of Michigan
item STANCAKOVA, ALENA - University Of Eastern Finland
item TEUMER, ALEXANDER - University Of Greifswald
item TUOMINEN, SAMULI - University Of Helsinki
item THERIAULT, SEBASTIEN - McMaster University
item VANGIPURAPU, JAGADISH - University Of Eastern Finland
item WHITFIELD, JOHN - Qimr Berghofer Medical Research Institute
item WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item YAO, JIE - Harbor-Ucla Medical Center
item YU, BING - University Of Texas Health Science Center
item ZHAO, WEI - University Of Michigan
item ARKING, DAN - Johns Hopkins University School Of Medicine
item AUVINEN, JUHA - University Of Oulu
item LIU, CHUNYU - Boston University School Of Public Health
item MANNIKKO, MINNA - University Of Oulu
item RISCH, LORENZ - University Of Bern
item ROTTER, JEROME - Harbor-Ucla Medical Center
item SNIEDER, HAROLD - University Of Groningen
item VEIJOLA, JUHA - University Of Oulu
item BLAKEMORE, ALEXANDRA - Imperial College
item BOEHNKE, MICHAEL - University Of Michigan
item CAMPBELL, HARRY - University Of Edinburgh
item CONEN, DAVID - McMaster University
item ERIKSSON, JOHAN - University Of Helsinki
item GRABE, HANS - University Of Greifswald
item GUO, XIUQING - Harbor-Ucla Medical Center
item VAN DER HARST, PIM - University Of Groningen
item HARTMAN, CATHARINA - University Of Groningen
item HAYWARD, CAROLINE - University Of Edinburgh
item HEATH, ANDREW - Washington University School Of Medicine
item JARVELIN, MARJO - Imperial College
item KAHONEN, MIKA - University Of Eastern Finland
item KARDIA, SHARON - University Of Eastern Finland
item KUHNE, MICHAEL - University Hospital Of Basel
item KUUSISTO, JOHANNA - University Of Eastern Finland
item LAAKSO, MARKKU - University Of North Carolina
item LAHTI, JARI - University Of Helsinki
item LEHTIMAKI, TERHO - University Of Tampere
item MCINTOSH, ANDREW - University Of Edinburgh
item MOHLKE, KAREN - University Of Washington
item MORRISON, ALANNA - University Of Texas Health Science Center
item MARTIN, NICHOLAS - Qimr Berghofer Medical Research Institute
item OLDEHINKEL, ALBERTINE - University Of Groningen
item PENNINX, BRENDA - University Of Amsterdam
item PSATY, BRUCE - University Of Washington
item RAITAKARI, OLLI - University Of Turku
item RUDAN, IGOR - University Of Edinburgh
item SAMANI, NILESH - University Of Leicester
item SCOTT, LAURA - University Of Michigan
item SPECTOR, TIM - King'S College
item VERWEIJ, NIEK - University Of Groningen
item WEIR, DAVID - University Of Michigan
item WILSON, JAMES - University Of Edinburgh
item LEVY, DANIEL - National Institutes Of Health (NIH)
item TZOULAKI, IOANNA - Imperial College
item BELL, JIMMY - University Of Utah
item MATTHEWS, PAUL - Imperial College
item ROTHENFLUH, ADRIAN - University Of Utah
item SCHUMANN, GUNTER - King'S College
item ELLIOTT, PAUL - Imperial College

Submitted to: Nature Human Behaviour
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2019
Publication Date: 9/1/2019
Citation: Evangelou, E., Gao, H., Chu, C., Nritsos, G., Blakeley, P., Butts, A.R., Pazoki, R., Suzuki, H., Koskeridis, F., Yiorkas, A.M., Karaman, I., Elliott, J., Luo, Q., Aeschbacher, S., Bartz, T.M., Baumeister, S.E., Braund, P.S., Brown, M.R., Brody, J.A., Clarke, T.K., Dimou, N., Faul, J.D., Homuth, G., Jackson, A.U., Kentistou, K.A., Joshi, P.K., Lemaitre, R.N., Lind, P.A., Lyytikainen, L.P., Mangino, M., Milaneschi, Y., Nelson, C.P., Nolte, I.M., Perala, M.M., Polasek, O., Porteous, D., Ratiff, S.M., Smith, J.A., Stancakova, A., Teumer, A., Tuominen, S., Theriault, S., Vangipurapu, J., Whitfield, J.B., Wood, A., Yao, J., Yu, B., Zhao, W., Arking, D.E., Auvinen, J., Liu, C., Mannikko, M., Risch, L., Rotter, J.I., Snieder, H., Veijola, J., Blakemore, A.I., Boehnke, M., Campbell, H., Conen, D., Eriksson, J.G., Grabe, H.J., Guo, X., Van Der Harst, P., Hartman, C.A., Hayward, C., Heath, A.C., Jarvelin, M.R., Kahonen, M., Kardia, S.L., Kuhne, M., Kuusisto, J., Laakso, M., Lahti, J., Lehtimaki, T., McIntosh, A.M., Mohlke, K.L., Morrison, A.C., Martin, N.G., Oldehinkel, A.J., Penninx, B.W., Psaty, B.M., Raitakari, O.T., Rudan, I., Samani, N.J., Scott, L.J., Spector, T.D., Verweij, N., Weir, D.R., Wilson, J.F., Levy, D., Tzoulaki, I., Bell, J.D., Matthews, P.M., Rothenfluh, A., Schumann, G., Elliott, P. 2019. New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders. Nature Human Behaviour. 3(9):950-961. https://doi.org/10.1038/s41562-019-0653-z.
DOI: https://doi.org/10.1038/s41562-019-0653-z

Interpretive Summary: Alcohol intake is a risk factor for obesity. Further, the negative sequelae associated with excessive alcohol intake, such as hypertension and cardiovascular disease, have stronger associations with alcohol intake in those with obesity compared to those without. If we can understand why some people drink more alcohol than others we may be able to use this information to better predict who may benefit from interventions to prevent excess alcohol intake. Alcohol intake reflects both genetic and environmental factors, and the genetic factors that influence alcohol intake, in particular, are poorly understood. In order to resolve this, the current study used data from nearly half a million adults and examined loci across the whole genome for their associations with alcohol intake. Forty-six new loci were identified which associated with alcohol intake, and as a whole, these loci tended to be involved with other neuropsychiatric disorders such as schizophrenia. These neuropsychiatric disorders are, in turn, characterized by specific patterns of performance across cognition tasks, suggesting that cognitive tests could eventually be used to reveal those at risk of excessive alcohol intake. This information will be useful for researchers who wish to gain a better understanding of how genes influence alcohol intake, but also for clinicians who now have better information on some of the characteristics of individuals who are more likely to increase their obesity risk via intake of excess alcohol. Eventually, this information could contribute to a risk stratification tool based on genetics, which would better identify who might benefit from prevention strategies which reduce obesity risk, and the risk of a host of other health problems, by preventing excess alcohol intake.

Technical Abstract: 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 (gd**-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.