Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.

Karlsson Linnér, R.; Biroli, P.; Kong, E.; Meddens, SFW; Wedow, R.; Fontana, M.A.; Lebreton, M.; Tino, S.P.; Abdellaoui, A.; Hammerschlag, A.R.; Nivard, M.G.; Okbay, A.; Rietveld, C.A.; Timshel, P.N.; Trzaskowski, M.; Vlaming, R.; Zünd, C.L.; Bao, Y.; Buzdugan, L.; Caplin, A.H.; Chen, C.Y.; Eibich, P.; Fontanillas, P.; Gonzalez, J.R.; Joshi, P.K.; Karhunen, V.; Kleinman, A.; Levin, R.Z.; Lill, C.M.; Meddens, G.A.; Muntané, G.; Sanchez-Roige, S.; Rooij, FJV; Taskesen, E.; Wu, Y.; Zhang, F.; Auton, A.; Boardman, J.D.; Clark, D.W.; Conlin, A.; Dolan, C.C.; Fischbacher, U.; Groenen, PJF; Harris, K.M.; Hasler, G.; Hofman, A.; Ikram, M.A.; Jain, S.; Karlsson, R.; Kessler, R.C.; Kooyman, M.; MacKillop, J.; Männikkö, M.; Morcillo-Suarez, C.; McQueen, M.B.; Schmidt, K.M.; Smart, M.C.; Sutter, M.; Thurik, A.R.; Uitterlinden, A.G.; White, J.; Wit, H.; Yang, J.; Bertram, L.; Boomsma, D.I.; Esko, T.; Fehr, E.; Hinds, D.A.; Johannesson, M.; Kumari, M.; Laibson, D.; Magnusson, PKE; Meyer, M.N.; Navarro, A.; Palmer, A.A.; Pers, T.H.; Posthuma, D.; Schunk, D.; Stein, M.B.; Svento, R.; Tiemeier, H.; Timmers, PRHJ; Turley, P.; Ursano, R.J.; Wagner, G.G.; Wilson, J.F.; Gratten, J.; Lee, J.J.; Cesarini, D.; Benjamin, D.J.; Koellinger, P.D.; Beauchamp, J.P.

doi:10.1038/s41588-018-0309-3

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.

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Serval ID

serval:BIB_48844D716164

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences.

Journal

Nature genetics

Author(s)

Karlsson Linnér R., Biroli P., Kong E., Meddens SFW, Wedow R., Fontana M.A., Lebreton M., Tino S.P., Abdellaoui A., Hammerschlag A.R., Nivard M.G., Okbay A., Rietveld C.A., Timshel P.N., Trzaskowski M., Vlaming R., Zünd C.L., Bao Y., Buzdugan L., Caplin A.H., Chen C.Y., Eibich P., Fontanillas P., Gonzalez J.R., Joshi P.K., Karhunen V., Kleinman A., Levin R.Z., Lill C.M., Meddens G.A., Muntané G., Sanchez-Roige S., Rooij FJV, Taskesen E., Wu Y., Zhang F., Auton A., Boardman J.D., Clark D.W., Conlin A., Dolan C.C., Fischbacher U., Groenen PJF, Harris K.M., Hasler G., Hofman A., Ikram M.A., Jain S., Karlsson R., Kessler R.C., Kooyman M., MacKillop J., Männikkö M., Morcillo-Suarez C., McQueen M.B., Schmidt K.M., Smart M.C., Sutter M., Thurik A.R., Uitterlinden A.G., White J., Wit H., Yang J., Bertram L., Boomsma D.I., Esko T., Fehr E., Hinds D.A., Johannesson M., Kumari M., Laibson D., Magnusson PKE, Meyer M.N., Navarro A., Palmer A.A., Pers T.H., Posthuma D., Schunk D., Stein M.B., Svento R., Tiemeier H., Timmers PRHJ, Turley P., Ursano R.J., Wagner G.G., Wilson J.F., Gratten J., Lee J.J., Cesarini D., Benjamin D.J., Koellinger P.D., Beauchamp J.P.

Working group(s)

23and Me Research Team, eQTLgen Consortium, International Cannabis Consortium, Social Science Genetic Association Consortium

Contributor(s)

Agee M., Alipanahi B., Bell R.K., Bryc K., Elson S.L., Furlotte N.A., Huber K.E., Litterman N.K., McCreight J.C., McIntyre M.H., Mountain J.L., Northover CAM, Pitts S.J., Sathirapongsasuti J.F., Sazonova O.V., Shelton J.F., Shringarpure S., Tian C., Tung J.Y., Vacic V., Wilson C.H., Agbessi M., Ahsan H., Alves I., Andiappan A., Awadalla P., Battle A., Beutner F., Jan Bonder M., Boomsma D.I., Christiansen M., Claringbould A., Deelen P., Esko T., Favé M.J., Franke L., Frayling T., Gharib S.A., Gibson G., Heijmans B., Hemani G., Jansen R., Kähönen M., Kalnapenkis A., Kasela S., Kettunen J., Kim Y., Kirsten H., Kovacs P., Krohn K., Kronberg-Guzman J., Kukushkina V., Kutalik Z., Lee B., Lehtimäki T., Loeffler M., Marigorta U.M., Metspalu A., Milani L., Montgomery G.W., Müller-Nurasyid M., Nauck M., Nivard M.G., Penninx B., Perola M., Pervjakova N., Pierce B., Powell J., Prokisch H., Psaty B.M., Raitakari O., Ring S., Ripatti S., Rotzchke O., Rüeger S., Saha A., Scholz M., Schramm K., Seppälä I., Stumvoll M., Sullivan P., Hoen P.T., Teumer A., Thiery J., Tong L., Tönjes A., Dongen J.V., Meurs J.V., Verlouw J., Visscher P.M., Völker U., Võsa U., Westra H.J., Yaghootkar H., Yang J., Zeng B., Zhang F., Okbay A., Beauchamp J.P., Fontana M.A., Lee J.J., Pers T.H., Rietveld C.A., Turley P., Chen G.B., Emilsson V., Meddens SFW, Oskarsson S., Pickrell J.K., Thom K., Timshel P., de Vlaming R., Abdellaoui A., Ahluwalia T.S., Bacelis J., Baumbach C., Bjornsdottir G., Brandsma J.H., Concas M.P., Derringer J., Furlotte N.A., Galesloot T.E., Girotto G., Gupta R., Hall L.M., Harris S.E., Hofer E., Horikoshi M., Huffman J.E., Kaasik K., Kalafati I.P., Karlsson R., Kong A., Lahti J., Lee SJV, de Leeuw C., Lind P.A., Lindgren K.O., Liu T., Mangino M., Marten J., Mihailov E., Miller M.B., Most PJV, Oldmeadow C., Payton A., Pervjakova N., Peyrot W.J., Qian Y., Raitakari O., Rueedi R., Salvi E., Schmidt B., Schraut K.E., Shi J., Smith A.V., Poot R.A., Pourcain B.S., Teumer A., Thorleifsson G., Verweij N., Vuckovic D., Wellmann J., Westra H.J., Yang J., Zhao W., Zhu Z., Alizadeh B.Z., Amin N., Bakshi A., Baumeister S.E., Biino G., Bønnelykke K., Boyle P.A., Campbell H., Cappuccio F.P., Davies G., De Neve J.E., Deloukas P., Demuth I., Ding J., Eibich P., Eisele L., Eklund N., Evans D.M., Faul J.D., Feitosa M.F., Forstner A.J., Gandin I., Gunnarsson B., Halldórsson B.V., Harris T.B., Heath A.C., Hocking L.J., Holliday E.G., Homuth G., Horan M.A., Hottenga J.J., de Jager P.L., Joshi P.K., Jugessur A., Kaakinen M.A., Kähönen M., Kanoni S., Keltigangas-Järvinen L., Kiemeney LALM, Kolcic I., Koskinen S., Kraja A.T., Kroh M., Kutalik Z., Latvala A., Launer L.J., Lebreton M.P., Levinson D.F., Lichtenstein P., Lichtner P., Liewald DCM, Loukola A., Madden P.A., Mägi R., Mäki-Opas T., Marioni R.E., Marques-Vidal P., Meddens G.A., McMahon G., Meisinger C., Meitinger T., Milaneschi Y., Milani L., Montgomery G.W., Myhre R., Nelson C.P., Nyholt D.R., Ollier WER, Palotie A., Paternoster L., Pedersen N.L., Petrovic K.E., Porteous D.J., Räikkönen K., Ring S.M., Robino A., Rostapshova O., Rudan I., Rustichini A., Salomaa V., Sanders A.R., Sarin A.P., Schmidt H., Scott R.J., Smith B.H., Smith J.A., Staessen J.A., Steinhagen-Thiessen E., Strauch K., Terracciano A., Tobin M.D., Ulivi S., Vaccargiu S., Quaye L., Rooij FJV, Venturini C., Vinkhuyzen AAE, Völker U., Völzke H., Vonk J.M., Vozzi D., Waage J., Ware E.B., Willemsen G., Attia J.R., Bennett D.A., Berger K., Bertram L., Bisgaard H., Boomsma D.I., Borecki I.B., Bültmann U., Chabris C.F., Cucca F., Cusi D., Deary I.J., Dedoussis G.V., Duijn CMV, Eriksson J.G., Franke B., Franke L., Gasparini P., Gejman P.V., Gieger C., Grabe H.J., Gratten J., Groenen PJF, Gudnason V., Harst P.V., Hayward C., Hinds D.A., Hoffmann W., Hyppönen E., Iacono W.G., Jacobsson B., Järvelin M.R., Jöckel K.H., Kaprio J., Kardia SLR, Lehtimäki T., Lehrer S.F., Magnusson PKE, Martin N.G., McGue M., Metspalu A., Pendleton N., Penninx B., Perola M., Pirastu N., Pirastu M., Polasek O., Posthuma D., Power C., Province M.A., Samani N.J., Schlessinger D., Schmidt R., Sørensen TIA, Spector T.D., Stefansson K., Thorsteinsdottir U., Thurik A.R., Timpson N.J., Tiemeier H., Tung J.Y., Uitterlinden A.G., Vitart V., Vollenweider P., Weir D.R., Wilson J.F., Wright A.F., Conley D.C., Krueger R.F., Smith G.D., Hofman A., Laibson D.I., Medland S.E., Meyer M.N., Yang J., Johannesson M., Visscher P.M., Esko T., Koellinger P.D., Cesarini D., Benjamin D.J.

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

02/2019

Peer-reviewed

Oui

Volume

Number

Pages

245-257

Language

english

Notes

Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over 1 million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. Across all GWAS, we identified hundreds of associated loci, including 99 loci associated with general risk tolerance. We report evidence of substantial shared genetic influences across risk tolerance and the risky behaviors: 46 of the 99 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is genetically correlated ([Formula: see text] ~ 0.25 to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near SNPs associated with general risk tolerance are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We found no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

Keywords

Behavior/physiology, Case-Control Studies, Female, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genetics, Behavioral/methods, Genome-Wide Association Study/methods, Genotype, Humans, Male, Polymorphism, Single Nucleotide/genetics

URN

urn:nbn:ch:serval-BIB_48844D7161647

OAI-PMH

oai:serval.unil.ch:BIB_48844D716164

DOI

10.1038/s41588-018-0309-3

Pubmed

30643258

Web of science

000457314300011

Create date

25/01/2019 9:33