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; 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; Futao Zhang; Adam Auton; Jason D Boardman; David W Clark; Andrew Conlin; Conor C Dolan; Urs Fischbacher; Patrick J F Groenen; Kathleen Mullan Harris; Gregor Hasler; Albert Hofman; Mohammad A Ikram; Sonia Jain; Robert Karlsson; Tune H. Pers; 23and Me Research Team

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

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 CaplinChia-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, Futao Zhang, Adam Auton, Jason D Boardman, David W Clark, Andrew Conlin, Conor C Dolan, Urs Fischbacher, Patrick J F Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A Ikram, Sonia Jain, Robert Karlsson, Tune H. Pers, 23and Me Research Team

105 Citations (Scopus)

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 language	English
Journal	Nature Genetics
Volume	51
Issue number	2
Pages (from-to)	245-257
Number of pages	13
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-018-0309-3
Publication status	Published - 1 Feb 2019

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Karlsson Linnér, R., Biroli, P., Kong, E., Meddens, S. F. W., 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. D., Zünd, C. L., Bao, Y., Buzdugan, L., ... 23and Me Research Team (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

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

Research output: Contribution to journal › Journal article › Research › peer-review

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, Zhang, F, Auton, A, Boardman, JD, Clark, DW, Conlin, A, Dolan, CC, Fischbacher, U, Groenen, PJF, Harris, KM, Hasler, G, Hofman, A, Ikram, MA, Jain, S, Karlsson, R, Pers, TH & 23and Me Research Team 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

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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 (∣{\^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.",

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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 - Zhang, Futao

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 - Pers, Tune H.

AU - 23and Me Research Team

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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.

U2 - 10.1038/s41588-018-0309-3

DO - 10.1038/s41588-018-0309-3

M3 - Journal article

C2 - 30643258

SN - 1061-4036

VL - 51

SP - 245

EP - 257

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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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