Dataset Information

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 ([Formula: see text]?~?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.

SUBMITTER: Karlsson Linner R

PROVIDER: S-EPMC6713272 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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 R Biroli Pietro P Kong Edward E Meddens S Fleur W SFW Wedow Robbee R Fontana Mark Alan MA Lebreton Maël M Tino Stephen P SP Abdellaoui Abdel A Hammerschlag Anke R AR Nivard Michel G MG Okbay Aysu A Rietveld Cornelius A CA Timshel Pascal N PN Trzaskowski Maciej M Vlaming Ronald de R Zünd Christian L CL Bao Yanchun Y Buzdugan Laura L Caplin Ann H AH Chen Chia-Yen CY Eibich Peter P Fontanillas Pierre P Gonzalez Juan R JR Joshi Peter K PK Karhunen Ville V Kleinman Aaron A Levin Remy Z RZ Lill Christina M CM Meddens Gerardus A GA Muntané Gerard G Sanchez-Roige Sandra S Rooij Frank J van FJV Taskesen Erdogan E Wu Yang Y Zhang Futao F Auton Adam A Boardman Jason D JD Clark David W DW Conlin Andrew A Dolan Conor C CC Fischbacher Urs U Groenen Patrick J F PJF Harris Kathleen Mullan KM Hasler Gregor G Hofman Albert A Ikram Mohammad A MA Jain Sonia S Karlsson Robert R Kessler Ronald C RC Kooyman Maarten M MacKillop James J Männikkö Minna M Morcillo-Suarez Carlos C McQueen Matthew B MB Schmidt Klaus M KM Smart Melissa C MC Sutter Matthias M Thurik A Roy AR Uitterlinden André G AG White Jon J Wit Harriet de H Yang Jian J Bertram Lars L Boomsma Dorret I DI Esko Tõnu T Fehr Ernst E Hinds David A DA Johannesson Magnus M Kumari Meena M Laibson David D Magnusson Patrik K E PKE Meyer Michelle N MN Navarro Arcadi A Palmer Abraham A AA Pers Tune H TH Posthuma Danielle D Schunk Daniel D Stein Murray B MB Svento Rauli R Tiemeier Henning H Timmers Paul R H J PRHJ Turley Patrick P Ursano Robert J RJ Wagner Gert G GG Wilson James F JF Gratten Jacob J Lee James J JJ Cesarini David D Benjamin Daniel J DJ Koellinger Philipp D PD Beauchamp Jonathan P JP

Nature genetics 20190114 2

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 b ...[more]

PMID: 30643258

Similar Datasets

Project description:BACKGROUND:Developing chilling tolerant accessions of domesticated Asian rice is a potential source of significant crop improvement. The uniquely chilling sensitive nature of the tropically originating Oryza sativa make it the most important cereal crop that can gain significantly from improved tolerance to low temperatures. However, mechanisms underlying this complex trait are not fully understood. Oryza sativa has two subspecies with different levels of chilling tolerance, JAPONICA and INDICA, providing an ideal tool to investigate mechanistic differences in the chilling stress tolerance responses within this important crop species. RESULTS:The Rice Diversity Panel 1 (RDP1) was used to investigate a core set of Oryza sativa accessions. The tools available for this panel allowed for a comprehensive analysis of two chilling tolerance traits at multiple temperatures across a 354-cultivar subset of the RDP1. Chilling tolerance trait values were distributed as mostly subpopulation specific clusters of Tolerant, Intermediate, and Sensitive accessions. Genome-wide association study (GWAS) mapping approaches using all 354 accessions yielded a total of 245 quantitative trait loci (QTL), containing 178 unique QTL covering 25% of the rice genome, while 40 QTL were identified by multiple traits. QTL mappings using subsets of rice accession clusters yielded another 255 QTL, for a total of 500 QTL. The genes within these multiple trait QTL were analyzed for Gene Ontology (GO) term and potential pathway enrichments. Terms related to "carbohydrate biosynthesis", "carbohydrate transmembrane transport", "small molecule protein modification", and "plasma membrane" were enriched from this list. Filtering was done to identify more likely candidate pathways involved in conferring chilling tolerance, resulting in enrichment of terms related to "Golgi apparatus", "stress response", "transmembrane transport", and "signal transduction". CONCLUSIONS:Taken together, these GO term clusters revealed a likely involvement of Golgi-mediated subcellular and extracellular vesicle and intracellular carbohydrate transport as a general cold stress tolerance response mechanism to achieve cell and metabolic homeostasis under chilling stress.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets