Genome-wide study identifies 611 loci associated with risk tolerance and risky behaviors

Karlsson Linner, R.; Biroli, P.; Kong, E.; Meddens, S. F. W.; Wedow, R.; Fontana, M. A.; Lebreton, M.; Abdellaoui, A.; Hammerschlag, A. R.; Nivard, M. G.; Okbay, A.; Rietveld, C. A.; Timshel, P. N.; Tino, S. P.; Trzaskowski, M.; de 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.; Muntane, G.; Sanchez-Roige, S.; van Rooij, F. J.; Taskesen, E.; Wu, Y.; Zhang, F.; 23andMe Research Team,; eQTLgen Consortium,; International Cannab

doi:10.1101/261081

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bioRxiv · 10.1101/261081

Genome-wide study identifies 611 loci associated with risk tolerance and risky behaviors

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Abstract

Humans vary substantially in their willingness to take risks. In a combined sample of over one 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. We identified 611 approximately independent genetic loci associated with at least one of our phenotypes, including 124 with general risk tolerance. We report evidence of substantial shared genetic influences across general risk tolerance and risky behaviors: 72 of the 124 general risk tolerance loci contain a lead SNP for at least one of our other GWAS, and general risk tolerance is moderately to strongly genetically correlated ([Formula] to 0.50) with a range of risky behaviors. Bioinformatics analyses imply that genes near general-risk-tolerance-associated SNPs are highly expressed in brain tissues and point to a role for glutamatergic and GABAergic neurotransmission. We find no evidence of enrichment for genes previously hypothesized to relate to risk tolerance.

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Karlsson Linner, R., Biroli, P., Kong, E., Meddens, S. F. W., Wedow, R., Fontana, M. A., Lebreton, M., Abdellaoui, A., Hammerschlag, A. R., Nivard, M. G., Okbay, A., Rietveld, C. A., Timshel, P. N., Tino, S. P., Trzaskowski, M., de 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., Muntane, G., Sanchez-Roige, S., van Rooij, F. J., Taskesen, E., Wu, Y., Zhang, F., 23andMe Research Team,, eQTLgen Consortium,, International Cannab. 2018-02-08. Genome-wide study identifies 611 loci associated with risk tolerance and risky behaviors. https://doi.org/10.1101/261081

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