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

Citation

Karlsson Linnér, Richard; Biroli, Pietro; Kong, Edward; Meddens, S. Fleur W.; Wedow, Robbee; Fontana, Mark Alan; Lebreton, Maël; Tino, Stephen P.; Abdellaoui, Abdel; & Hammerschlag, Anke R., et al. (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.

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 (|r^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.

URL

https://doi.org/10.1038/s41588-018-0309-3

Reference Type

Journal Article

Journal Title

Nature Genetics

Author(s)

Karlsson Linnér, Richard
Biroli, Pietro
Kong, Edward
Meddens, S. Fleur W.
Wedow, Robbee
Fontana, Mark Alan
Lebreton, Maël
Tino, Stephen P.
Abdellaoui, Abdel
Hammerschlag, Anke R.
Nivard, Michel G.
Okbay, Aysu
Rietveld, Cornelius A.
Timshel, Pascal N.
Trzaskowski, Maciej
Vlaming, Ronald de
Zünd, Christian L.
Bao, Yanchun
Buzdugan, Laura
Caplin, Ann H.
Chen, Chia-Yen
Eibich, Peter
Fontanillas, Pierre
Gonzalez, Juan R.
Joshi, Peter K.
Karhunen, Ville
Kleinman, Aaron
Levin, Remy Z.
Lill, Christina M.
Meddens, Gerardus A.
Muntané, Gerard
Sanchez-Roige, Sandra
Rooij, Frank J. van
Taskesen, Erdogan
Wu, Yang
Zhang, Futao
Agee, Michelle
Alipanahi, Babak
Bell, Robert K.
Bryc, Katarzyna
Elson, Sarah L.
Furlotte, Nicholas A.
Huber, Karen E.
Litterman, Nadia K.
McCreight, Jennifer C.
McIntyre, Matthew H.
Mountain, Joanna L.
Northover, Carrie A. M.
Pitts, Steven J.
Sathirapongsasuti, J. Fah
Sazonova, Olga V.
Shelton, Janie F.
Shringarpure, Suyash
Tian, Chao
Tung, Joyce Y.
Vacic, Vladimir
Wilson, Catherine H.
Agbessi, Mawussé
Ahsan, Habibul
Alves, Isabel
Andiappan, Anand
Awadalla, Philip
Battle, Alexis
Beutner, Frank
Jan Bonder, Marc
Boomsma, Dorret I.
Christiansen, Mark
Claringbould, Annique
Deelen, Patrick
Esko, Tõnu
Favé, Marie-Julie
Franke, Lude
Frayling, Timothy
Gharib, Sina A.
Gibson, Gregory
Heijmans, Bastiaan
Hemani, Gibran
Jansen, Rick
Kähönen, Mika
Kalnapenkis, Anette
Kasela, Silva
Kettunen, Johannes
Kim, Yungil
Kirsten, Holger
Kovacs, Peter
Krohn, Knut
Kronberg-Guzman, Jaanika
Kukushkina, Viktorija
Kutalik, Zoltan
Lee, Bernett
Lehtimäki, Terho
Loeffler, Markus
Marigorta, Urko M.
Metspalu, Andres
Milani, Lili
Montgomery, Grant W.
Müller-Nurasyid, Martina
Nauck, Matthias
Nivard, Michel G.
Penninx, Brenda
Perola, Markus
Pervjakova, Natalia
Pierce, Brandon
Powell, Joseph
Prokisch, Holger
Psaty, Bruce M.
Raitakari, Olli
Ring, Susan
Ripatti, Samuli
Rotzchke, Olaf
Rüeger, Sina
Saha, Ashis
Scholz, Markus
Schramm, Katharina
Seppälä, Ilkka
Stumvoll, Michael
Sullivan, Patrick
Hoen, Peter-Bram t
Teumer, Alexander
Thiery, Joachim
Tong, Lin
Tönjes, Anke
Dongen, Jenny van
Meurs, Joyce van
Verlouw, Joost
Visscher, Peter M.
Völker, Uwe
Võsa, Urmo
Westra, Harm-Jan
Yaghootkar, Hanieh
Yang, Jian
Zeng, Biao
Zhang, Futao
Okbay, Aysu
Beauchamp, Jonathan P.
Fontana, Mark Alan
Lee, James J.
Pers, Tune H.
Rietveld, Cornelius A.
Turley, Patrick
Chen, Guo-Bo
Emilsson, Valur
Meddens, S. Fleur W.
Oskarsson, Sven
Pickrell, Joseph K.
Thom, Kevin
Timshel, Pascal
de Vlaming, Ronald
Abdellaoui, Abdel
Ahluwalia, Tarunveer S.
Bacelis, Jonas
Baumbach, Clemens
Bjornsdottir, Gyda
Brandsma, Johannes H.
Concas, Maria Pina
Derringer, Jaime
Furlotte, Nicholas A.
Galesloot, Tessel E.
Girotto, Giorgia
Gupta, Richa
Hall, Leanne M.
Harris, Sarah E.
Hofer, Edith
Horikoshi, Momoko
Huffman, Jennifer E.
Kaasik, Kadri
Kalafati, Ioanna P.
Karlsson, Robert
Kong, Augustine
Lahti, Jari
Lee, Sven J. van der
de Leeuw, Christiaan
Lind, Penelope A.
Lindgren, Karl-Oskar
Liu, Tian
Mangino, Massimo
Marten, Jonathan
Mihailov, Evelin
Miller, Michael B.
Most, Peter J. van der
Oldmeadow, Christopher
Payton, Antony
Pervjakova, Natalia
Peyrot, Wouter J.
Qian, Yong
Raitakari, Olli
Rueedi, Rico
Salvi, Erika
Schmidt, Börge
Schraut, Katharina E.
Shi, Jianxin
Smith, Albert V.
Poot, Raymond A.
Pourcain, Beate St
Teumer, Alexander
Thorleifsson, Gudmar
Verweij, Niek
Vuckovic, Dragana
Wellmann, Juergen
Westra, Harm-Jan
Yang, Jingyun
Zhao, Wei
Zhu, Zhihong
Alizadeh, Behrooz Z.
Amin, Najaf
Bakshi, Andrew
Baumeister, Sebastian E.
Biino, Ginevra
Bønnelykke, Klaus
Boyle, Patricia A.
Campbell, Harry
Cappuccio, Francesco P.
Davies, Gail
De Neve, Jan-Emmanuel
Deloukas, Panos
Demuth, Ilja
Ding, Jun
Eibich, Peter
Eisele, Lewin
Eklund, Niina
Evans, David M.
Faul, Jessica D.
Feitosa, Mary F.
Forstner, Andreas J.
Gandin, Ilaria
Gunnarsson, Bjarni
Halldórsson, Bjarni V.
Harris, Tamara B.
Heath, Andrew C.
Hocking, Lynne J.
Holliday, Elizabeth G.
Homuth, Georg
Horan, Michael A.
Hottenga, Jouke-Jan
de Jager, Philip L.
Joshi, Peter K.
Jugessur, Astanand
Kaakinen, Marika A.
Kähönen, Mika
Kanoni, Stavroula
Keltigangas-Järvinen, Liisa
Kiemeney, Lambertus A. L. M.
Kolcic, Ivana
Koskinen, Seppo
Kraja, Aldi T.
Kroh, Martin
Kutalik, Zoltan
Latvala, Antti
Launer, Lenore J.
Lebreton, Maël P.
Levinson, Douglas F.
Lichtenstein, Paul
Lichtner, Peter
Liewald, David C. M.
Loukola, Anu
Madden, Pamela A.
Mägi, Reedik
Mäki-Opas, Tomi
Marioni, Riccardo E.
Marques-Vidal, Pedro
Meddens, Gerardus A.
McMahon, George
Meisinger, Christa
Meitinger, Thomas
Milaneschi, Yusplitri
Milani, Lili
Montgomery, Grant W.
Myhre, Ronny
Nelson, Christopher P.
Nyholt, Dale R.
Ollier, William E. R.
Palotie, Aarno
Paternoster, Lavinia
Pedersen, Nancy L.
Petrovic, Katja E.
Porteous, David J.
Räikkönen, Katri
Ring, Susan M.
Robino, Antonietta
Rostapshova, Olga
Rudan, Igor
Rustichini, Aldo
Salomaa, Veikko
Sanders, Alan R.
Sarin, Antti-Pekka
Schmidt, Helena
Scott, Rodney J.
Smith, Blair H.
Smith, Jennifer A.
Staessen, Jan A.
Steinhagen-Thiessen, Elisabeth
Strauch, Konstantin
Terracciano, Antonio
Tobin, Martin D.
Ulivi, Sheila
Vaccargiu, Simona
and Me Research, Team
e, QTLgen Consortium
International Cannabis, Consortium
Social Science Genetic Association, Consortium

Year Published

2019

ISSN/ISBN

1546-1718

DOI

10.1038/s41588-018-0309-3

Reference ID

5972