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

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

Research output: Contribution to JournalArticleAcademicpeer-review

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 (∣r̂ g∣ ~ 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.

Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalNature Genetics
Volume51
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

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Genetic Loci
Genome-Wide Association Study
Single Nucleotide Polymorphism
Computational Biology
Synaptic Transmission
Genes
Smoking
Brain

Cite this

Social Science Genetic Association Consortium, 23and Me Research Team, eQTLGen Consortium, & International Cannabis Consortium (2019). Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nature Genetics, 51(2), 245-257. https://doi.org/10.1038/s41588-018-0309-3
Social Science Genetic Association Consortium ; 23and Me Research Team ; eQTLGen Consortium ; International Cannabis Consortium. / Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. In: Nature Genetics. 2019 ; Vol. 51, No. 2. pp. 245-257.
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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 (∣r̂ g∣ ~ 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.",
author = "{Karlsson Linn{\'e}r}, Richard and Pietro Biroli and Edward Kong and Meddens, {S. Fleur W.} and Robbee Wedow and Fontana, {Mark Alan} and Ma{\"e}l Lebreton and Tino, {Stephen P.} and Abdel Abdellaoui and Hammerschlag, {Anke R.} and Nivard, {Michel G.} and Aysu Okbay and Rietveld, {Cornelius A.} and Timshel, {Pascal N.} and Maciej Trzaskowski and Vlaming, {Ronald de} and Z{\"u}nd, {Christian L.} and Yanchun Bao and Laura Buzdugan and Caplin, {Ann H.} and Chen, {Chia Yen} and Peter Eibich and Pierre Fontanillas and Gonzalez, {Juan R.} and Joshi, {Peter K.} and Ville Karhunen and Aaron Kleinman and Levin, {Remy Z.} and Lill, {Christina M.} and Meddens, {Gerardus A.} and Gerard Muntan{\'e} and Sandra Sanchez-Roige and Rooij, {Frank J.van} and Erdogan Taskesen and Yang Wu and Futao Zhang and Michelle Agee and Babak Alipanahi and Bell, {Robert K.} and Katarzyna Bryc and Elson, {Sarah L.} and Furlotte, {Nicholas A.} and Huber, {Karen E.} and Litterman, {Nadia K.} and McCreight, {Jennifer C.} and McIntyre, {Matthew H.} and Mountain, {Joanna L.} and Northover, {Carrie A.M.} and Pitts, {Steven J.} and Sathirapongsasuti, {J. Fah} and Sazonova, {Olga V.} and Shelton, {Janie F.} and Suyash Shringarpure and Chao Tian and Tung, {Joyce Y.} and Vladimir Vacic and Wilson, {Catherine H.} and Mawuss{\'e} Agbessi and Habibul Ahsan and Isabel Alves and Anand Andiappan and Philip Awadalla and Alexis Battle and Frank Beutner and {Jan Bonder}, Marc and Boomsma, {Dorret I.} and Mark Christiansen and Annique Claringbould and Patrick Deelen and T{\~o}nu Esko and Fav{\'e}, {Marie Julie} and Lude Franke and Timothy Frayling and Gharib, {Sina A.} and Gregory Gibson and Bastiaan Heijmans and Gibran Hemani and Rick Jansen and Mika K{\"a}h{\"o}nen and Anette Kalnapenkis and Silva Kasela and Johannes Kettunen and Yungil Kim and Holger Kirsten and Peter Kovacs and Knut Krohn and Jaanika Kronberg-Guzman and Viktorija Kukushkina and Zoltan Kutalik and Bernett Lee and Terho Lehtim{\"a}ki and Markus Loeffler and Marigorta, {Urko M.} and Andres Metspalu and Lili Milani and Montgomery, {Grant W.} and Martina M{\"u}ller-Nurasyid and Matthias Nauck and Nivard, {Michel G.} and Brenda Penninx and Markus Perola and Natalia Pervjakova and Brandon Pierce and Joseph Powell and Holger Prokisch and Psaty, {Bruce M.} and Olli Raitakari and Ring, {Susan M.} and Samuli Ripatti and Olaf Rotzchke and Sina R{\"u}eger and Ashis Saha and Markus Scholz and Katharina Schramm and Ilkka Sepp{\"a}l{\"a} and Michael Stumvoll and Patrick Sullivan and Hoen, {Peter Bram t.} and Alexander Teumer and Joachim Thiery and Lin Tong and Anke T{\"o}njes and Dongen, {Jenny van} and Meurs, {Joyce van} and Joost Verlouw and Visscher, {Peter M.} and Uwe V{\"o}lker and Urmo V{\~o}sa and Westra, {Harm Jan} and Hanieh Yaghootkar and Jian Yang and Biao Zeng and Futao Zhang and Aysu Okbay and Beauchamp, {Jonathan P.} and Fontana, {Mark Alan} and Lee, {James J.} and Pers, {Tune H.} and Rietveld, {Cornelius A.} and Patrick Turley and Chen, {Guo Bo} and Valur Emilsson and Meddens, {S. Fleur W.} and Sven Oskarsson and Pickrell, {Joseph K.} and Kevin Thom and Pascal Timshel and {de Vlaming}, Ronald and Abdel Abdellaoui and Ahluwalia, {Tarunveer S.} and Jonas Bacelis and Clemens Baumbach and Gyda Bjornsdottir and Brandsma, {Johannes H.} and Concas, {Maria Pina} and Jaime Derringer and Furlotte, {Nicholas A.} and Galesloot, {Tessel E.} and Giorgia Girotto and Richa Gupta and Hall, {Leanne M.} and Harris, {Sarah E.} and Edith Hofer and Momoko Horikoshi and Huffman, {Jennifer E.} and Kadri Kaasik and Kalafati, {Ioanna P.} and Robert Karlsson and Augustine Kong and Jari Lahti and Lee, {Sven J.van der} and {de Leeuw}, Christiaan and Lind, {Penelope A.} and Lindgren, {Karl Oskar} and Tian Liu and Massimo Mangino and Jonathan Marten and Evelin Mihailov and Miller, {Michael B.} and Most, {Peter J.van der} and Christopher Oldmeadow and Antony Payton and Natalia Pervjakova and Peyrot, {Wouter J.} and Yong Qian and Olli Raitakari and Rico Rueedi and Erika Salvi and B{\"o}rge Schmidt and Schraut, {Katharina E.} and Jianxin Shi and Smith, {Albert V.} and Poot, {Raymond A.} and Pourcain, {Beate St} and Alexander Teumer and Gudmar Thorleifsson and Niek Verweij and Dragana Vuckovic and Juergen Wellmann and Westra, {Harm Jan} and Jingyun Yang and Wei Zhao and Zhihong Zhu and Alizadeh, {Behrooz Z.} and Najaf Amin and Andrew Bakshi and Baumeister, {Sebastian E.} and Ginevra Biino and Klaus B{\o}nnelykke and Boyle, {Patricia A.} and Harry Campbell and Cappuccio, {Francesco P.} and Gail Davies and {De Neve}, {Jan Emmanuel} and Panos Deloukas and Ilja Demuth and Jun Ding and Peter Eibich and Lewin Eisele and Niina Eklund and Evans, {David M.} and Faul, {Jessica D.} and Feitosa, {Mary F.} and Forstner, {Andreas J.} and Ilaria Gandin and Bjarni Gunnarsson and Halld{\'o}rsson, {Bjarni V.} and Harris, {Tamara B.} and Heath, {Andrew C.} and Hocking, {Lynne J.} and Holliday, {Elizabeth G.} and Georg Homuth and Horan, {Michael A.} and Hottenga, {Jouke Jan} and {de Jager}, {Philip L.} and Joshi, {Peter K.} and Astanand Jugessur and Kaakinen, {Marika A.} and Mika K{\"a}h{\"o}nen and Stavroula Kanoni and Liisa Keltigangas-J{\"a}rvinen and Kiemeney, {Lambertus A.L.M.} and Ivana Kolcic and Seppo Koskinen and Kraja, {Aldi T.} and Martin Kroh and Zoltan Kutalik and Antti Latvala and Launer, {Lenore J.} and Lebreton, {Ma{\"e}l P.} and Levinson, {Douglas F.} and Paul Lichtenstein and Peter Lichtner and Liewald, {David C.M.} and Anu Loukola and Madden, {Pamela A.} and Reedik M{\"a}gi and Tomi M{\"a}ki-Opas and Marioni, {Riccardo E.} and Pedro Marques-Vidal and Meddens, {Gerardus A.} and George McMahon and Christa Meisinger and Thomas Meitinger and Yusplitri Milaneschi and Lili Milani and Montgomery, {Grant W.} and Ronny Myhre and Nelson, {Christopher P.} and Nyholt, {Dale R.} and Ollier, {William E.R.} and Aarno Palotie and Lavinia Paternoster and Pedersen, {Nancy L.} and Petrovic, {Katja E.} and Porteous, {David J.} and Katri R{\"a}ikk{\"o}nen and Ring, {Susan M.} and Antonietta Robino and Olga Rostapshova and Igor Rudan and Aldo Rustichini and Veikko Salomaa and Sanders, {Alan R.} and Sarin, {Antti Pekka} and Helena Schmidt and Scott, {Rodney J.} and Smith, {Blair H.} and Smith, {Jennifer A.} and Staessen, {Jan A.} and Elisabeth Steinhagen-Thiessen and Konstantin Strauch and Antonio Terracciano and Tobin, {Martin D.} and Sheila Ulivi and Simona Vaccargiu and Lydia Quaye and Rooij, {Frank J.van} and Cristina Venturini and Vinkhuyzen, {Anna A.E.} and Uwe V{\"o}lker and Henry V{\"o}lzke and Vonk, {Judith M.} and Diego Vozzi and Johannes Waage and Ware, {Erin B.} and Gonneke Willemsen and Attia, {John R.} and Bennett, {David A.} and Klaus Berger and Lars Bertram and Hans Bisgaard and Boomsma, {Dorret I.} and Borecki, {Ingrid B.} and Ute B{\"u}ltmann and Chabris, {Christopher F.} and Francesco Cucca and Daniele Cusi and Deary, {Ian J.} and Dedoussis, {George V.} and Duijn, {Cornelia M.van} and Eriksson, {Johan G.} and Barbara Franke and Lude Franke and Paolo Gasparini and Gejman, {Pablo V.} and Christian Gieger and Grabe, {Hans J{\"o}rgen} and Jacob Gratten and Groenen, {Patrick J.F.} and Vilmundur Gudnason and Harst, {Pim van der} and Caroline Hayward and Hinds, {David A.} and Wolfgang Hoffmann and Elina Hypp{\"o}nen and Iacono, {William G.} and Bo Jacobsson and J{\"a}rvelin, {Marjo Riitta} and J{\"o}ckel, {Karl Heinz} and Jaakko Kaprio and Kardia, {Sharon L.R.} and Terho Lehtim{\"a}ki and Lehrer, {Steven F.} and Magnusson, {Patrik K.E.} and Martin, {Nicholas G.} and Matt McGue and Andres Metspalu and Neil Pendleton and Brenda Penninx and Markus Perola and Nicola Pirastu and Mario Pirastu and Ozren Polasek and Danielle Posthuma and Christine Power and Province, {Michael A.} and Samani, {Nilesh J.} and David Schlessinger and Reinhold Schmidt and S{\o}rensen, {Thorkild I.A.} and Spector, {Tim D.} and Kari Stefansson and Unnur Thorsteinsdottir and Thurik, {A. 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Social Science Genetic Association Consortium, 23and Me Research Team, eQTLGen Consortium & International Cannabis Consortium 2019, 'Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences' Nature Genetics, vol. 51, no. 2, pp. 245-257. https://doi.org/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. / Social Science Genetic Association Consortium; 23and Me Research Team; eQTLGen Consortium; International Cannabis Consortium.

In: Nature Genetics, Vol. 51, No. 2, 01.02.2019, p. 245-257.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Polasek, Ozren

AU - Posthuma, Danielle

AU - Power, Christine

AU - Province, Michael A.

AU - Samani, Nilesh J.

AU - Schlessinger, David

AU - Schmidt, Reinhold

AU - Sørensen, Thorkild I.A.

AU - Spector, Tim D.

AU - Stefansson, Kari

AU - Thorsteinsdottir, Unnur

AU - Thurik, A. Roy

AU - Timpson, Nicholas J.

AU - Tiemeier, Henning

AU - Tung, Joyce Y.

AU - Uitterlinden, André G.

AU - Vitart, Veronique

AU - Vollenweider, Peter

AU - Weir, David R.

AU - Wilson, James F.

AU - Wright, Alan F.

AU - Conley, Dalton C.

AU - Krueger, Robert F.

AU - Smith, George Davey

AU - Hofman, Albert

AU - Laibson, David

AU - Medland, Sarah E.

AU - Meyer, Michelle N.

AU - Yang, Jian

AU - Johannesson, Magnus

AU - Visscher, Peter M.

AU - Esko, Tõnu

AU - Koellinger, Philipp D.

AU - Cesarini, David

AU - Benjamin, Daniel J.

AU - Auton, Adam

AU - Boardman, Jason D.

AU - Clark, David W.

AU - Conlin, Andrew

AU - Dolan, Conor C.

AU - Fischbacher, Urs

AU - Groenen, Patrick J.F.

AU - Harris, Kathleen Mullan

AU - Hasler, Gregor

AU - Hofman, Albert

AU - Ikram, Mohammad A.

AU - Jain, Sonia

AU - Karlsson, Robert

AU - Kessler, Ronald C.

AU - Kooyman, Maarten

AU - MacKillop, James

AU - Männikkö, Minna

AU - Morcillo-Suarez, Carlos

AU - McQueen, Matthew B.

AU - Schmidt, Klaus M.

AU - Smart, Melissa C.

AU - Sutter, Matthias

AU - Thurik, A. Roy

AU - Uitterlinden, André G.

AU - White, Jon

AU - Wit, Harriet de

AU - Yang, Jian

AU - Bertram, Lars

AU - Boomsma, Dorret I.

AU - Esko, Tõnu

AU - Fehr, Ernst

AU - Hinds, David A.

AU - Johannesson, Magnus

AU - Kumari, Meena

AU - Laibson, David

AU - Magnusson, Patrik K.E.

AU - Meyer, Michelle N.

AU - Navarro, Arcadi

AU - Palmer, Abraham A.

AU - Pers, Tune H.

AU - Posthuma, Danielle

AU - Schunk, Daniel

AU - Stein, Murray B.

AU - Svento, Rauli

AU - Tiemeier, Henning

AU - Timmers, Paul R.H.J.

AU - Turley, Patrick

AU - Ursano, Robert J.

AU - Wagner, Gert G.

AU - Wilson, James F.

AU - Gratten, Jacob

AU - Lee, James J.

AU - Cesarini, David

AU - Benjamin, Daniel J.

AU - Koellinger, Philipp D.

AU - Beauchamp, Jonathan P.

AU - Social Science Genetic Association Consortium

AU - 23and Me Research Team

AU - eQTLGen Consortium

AU - International Cannabis Consortium

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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 (∣r̂ g∣ ~ 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.

AB - 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 (∣r̂ g∣ ~ 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.

UR - http://www.scopus.com/inward/record.url?scp=85060083196&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060083196&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0309-3

DO - 10.1038/s41588-018-0309-3

M3 - Article

VL - 51

SP - 245

EP - 257

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -

Social Science Genetic Association Consortium, 23and Me Research Team, eQTLGen Consortium, International Cannabis Consortium. Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences. Nature Genetics. 2019 Feb 1;51(2):245-257. https://doi.org/10.1038/s41588-018-0309-3