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Record W3099423124 · doi:10.1101/261081

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

2018· preprint· en· W3099423124 on OpenAlexaff
Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S. Fleur W. Meddens, Robbee Wedow, Mark Alan Fontana, Maël P. Lebreton, Abdel Abdellaoui, Anke R. Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A. Rietveld, Pascal Timshel, Stephen P. Tino, Maciej Trzaskowski, Ronald de Vlaming, Christian 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.A. van Rooij, Erdogan Taskesen, Yang Wu, Futao Zhang, Adam Auton, David W. Clark, Andrew Conlin, Conor Dolan, Urs Fischbacher, Patrick J. F. Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, M. Arfan Ikram, Sonia Jain, Robert Karlsson, Ronald C. Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suárez, Matthew B. McQueen, Klaus M. Schmidt, Melissa Smart, Matthias Sutter, Roy Thurik, André G. Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret I. Boomsma, Tõnu Esko, Ernst Fehr, David A. Hinds, Magnus Johannesson, Meena Kumari, David Laibson, Patrik K. E. Magnusson, Michelle N. Meyer, Arcadi Navarro, Abraham A. Palmer, Tune H. Pers, Daniëlle Posthuma, 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 Koellinger, Jonathan Beauchamp

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2018
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsSt. Joseph’s Healthcare HamiltonHomewood Research InstituteCentre for Global Health ResearchMcMaster UniversityUniversity of Toronto
FundersNational Institute on AgingNational Institutes of HealthMedical Research CouncilVetenskapsrådetUniversity of Southern California
KeywordsGenome-wide association studyBiologyGeneticsGenetic associationSNPSingle-nucleotide polymorphismGeneGenotype

Abstract

fetched live from OpenAlex

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 ( 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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.020

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.274
Teacher spread0.258 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations87
Published2018
Admission routes1
Has abstractyes

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Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenetic Associations and EpidemiologyFrench-language works237,207