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

Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S. Fleur W. Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Stephen P. Tino, Abdel Abdellaoui, Anke R. Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A. Rietveld, Pascal N. Timshel, Maciej Trzaskowski, Ronald de Vlaming, Christian L. Zünd, Yanchun Bao, Laura Buzdugan, Ann H. Caplin & 37 others Chia-Yen Chen, Peter Eibich, Pierre Fontanillas, Juan R. Gonzalez, Peter K. Joshi, Ville Karhunen, Aaron Kleinman, Remy Z. Levin, Christina M. Lill, Gerardus A. Meddens, Gerard Muntané, Sandra Sanchez-Roige, Frank J. van Rooij, Erdogan Taskesen, Yang Wu, Rick Jansen, Brenda Penninx, Wouter J. Peyrot, David M. Evans, Yuri Milaneschi, Danielle Posthuma, 23and Me Research Team, Daniel Schunk, Murray B Stein, Rauli Svento, Henning Tiemeier, Paul R. H. J. Timmers, Patrick Turley, Robert J. Ursano, Gert G. Wagner, James F. Wilson, Jacob Gratten, James J. Lee, David Cesarini, Daniel J. Benjamin, Philipp D. Koellinger, Jonathan P. Beauchamp

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
Early online date2019
DOIs
Publication statusPublished - 1 Feb 2019

Cite this

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 ; Jansen, Rick ; Penninx, Brenda ; Peyrot, Wouter J. ; Evans, David M. ; Milaneschi, Yuri ; Posthuma, Danielle ; 23and Me Research Team ; Schunk, Daniel ; Stein, Murray B ; Svento, Rauli ; Tiemeier, Henning ; Timmers, Paul R. H. J. ; Turley, Patrick ; Ursano, Robert J. ; Wagner, Gert G. ; Wilson, James F. ; Gratten, Jacob ; Lee, James J. ; Cesarini, David ; Benjamin, Daniel J. ; Koellinger, Philipp D. ; Beauchamp, Jonathan P. / 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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title = "Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences",
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 Chia-Yen Chen 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 Rick Jansen and Brenda Penninx and Peyrot, {Wouter J.} and Evans, {David M.} and Yuri Milaneschi and Danielle Posthuma and {23and Me Research Team} and Daniel Schunk and Stein, {Murray B} and Rauli Svento and Henning Tiemeier and Timmers, {Paul R. H. J.} and Patrick Turley and Ursano, {Robert J.} and Wagner, {Gert G.} and Wilson, {James F.} and Jacob Gratten and Lee, {James J.} and David Cesarini and Benjamin, {Daniel J.} and Koellinger, {Philipp D.} and Beauchamp, {Jonathan P.}",
year = "2019",
month = "2",
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doi = "10.1038/s41588-018-0309-3",
language = "English",
volume = "51",
pages = "245--257",
journal = "Nature Genetics",
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Karlsson Linnér, R, Biroli, P, Kong, E, Meddens, SFW, Wedow, R, Fontana, MA, Lebreton, M, Tino, SP, Abdellaoui, A, Hammerschlag, AR, Nivard, MG, Okbay, A, Rietveld, CA, Timshel, PN, Trzaskowski, M, Vlaming, RD, Zünd, CL, Bao, Y, Buzdugan, L, Caplin, AH, Chen, C-Y, Eibich, P, Fontanillas, P, Gonzalez, JR, Joshi, PK, Karhunen, V, Kleinman, A, Levin, RZ, Lill, CM, Meddens, GA, Muntané, G, Sanchez-Roige, S, Rooij, FJV, Taskesen, E, Wu, Y, Jansen, R, Penninx, B, Peyrot, WJ, Evans, DM, Milaneschi, Y, Posthuma, D, 23and Me Research Team, Schunk, D, Stein, MB, Svento, R, Tiemeier, H, Timmers, PRHJ, Turley, P, Ursano, RJ, Wagner, GG, Wilson, JF, Gratten, J, Lee, JJ, Cesarini, D, Benjamin, DJ, Koellinger, PD & Beauchamp, JP 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. / 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; Jansen, Rick; Penninx, Brenda; Peyrot, Wouter J.; Evans, David M.; Milaneschi, Yuri; Posthuma, Danielle; 23and Me Research Team; Schunk, Daniel; Stein, Murray B; Svento, Rauli; Tiemeier, Henning; Timmers, Paul R. H. J.; Turley, Patrick; Ursano, Robert J.; Wagner, Gert G.; Wilson, James F.; Gratten, Jacob; Lee, James J.; Cesarini, David; Benjamin, Daniel J.; Koellinger, Philipp D.; Beauchamp, Jonathan P.

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

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences

AU - Karlsson Linnér, Richard

AU - Biroli, Pietro

AU - Kong, Edward

AU - Meddens, S. Fleur W.

AU - Wedow, Robbee

AU - Fontana, Mark Alan

AU - Lebreton, Maël

AU - Tino, Stephen P.

AU - Abdellaoui, Abdel

AU - Hammerschlag, Anke R.

AU - Nivard, Michel G.

AU - Okbay, Aysu

AU - Rietveld, Cornelius A.

AU - Timshel, Pascal N.

AU - Trzaskowski, Maciej

AU - Vlaming, Ronald de

AU - Zünd, Christian L.

AU - Bao, Yanchun

AU - Buzdugan, Laura

AU - Caplin, Ann H.

AU - Chen, Chia-Yen

AU - Eibich, Peter

AU - Fontanillas, Pierre

AU - Gonzalez, Juan R.

AU - Joshi, Peter K.

AU - Karhunen, Ville

AU - Kleinman, Aaron

AU - Levin, Remy Z.

AU - Lill, Christina M.

AU - Meddens, Gerardus A.

AU - Muntané, Gerard

AU - Sanchez-Roige, Sandra

AU - Rooij, Frank J. van

AU - Taskesen, Erdogan

AU - Wu, Yang

AU - Jansen, Rick

AU - Penninx, Brenda

AU - Peyrot, Wouter J.

AU - Evans, David M.

AU - Milaneschi, Yuri

AU - Posthuma, Danielle

AU - 23and Me Research Team

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.

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.

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EP - 257

JO - Nature Genetics

JF - Nature Genetics

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