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Record W4376630890 · doi:10.1038/s41398-023-02453-y

CADM2 is implicated in impulsive personality and numerous other traits by genome- and phenome-wide association studies in humans and mice

2023· article· en· W4376630890 on OpenAlex
Sandra Sanchez‐Roige, Mariela Jennings, Hayley H. A. Thorpe, Jazlene E. Mallari, Lieke C van der Werf, Sevim B. Bianchi, Yuye Huang, Calvin Lee, Travis T. Mallard, Samuel A. Barnes, Jin Yi Wu, Amanda M. Barkley‐Levenson, Ely Cheikh Boussaty, Cedric E. Snethlage, Danielle Schafer, Zeljana Babic, Boyer D. Winters, Katherine Watters, Thomas Biederer, Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Daniella Coker, Gabriel Cuéllar-Partida, Devika Dhamija, Sayantan Das, Teresa Filshtein, Kipper Fletez‐Brant, Will Freyman, Karl Heilbron, Pooja Gandhi, Barry Hicks, David A. Hinds, Ethan M. Jewett, Yunxuan Jiang, Katelyn Kukar, Keng‐Han Lin, Maya Lowe, Jey C. McCreight, Matthew H. McIntyre, Steven J. Micheletti, Meghan E. Moreno, Joanna L. Mountain, Priyanka Nandakumar, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petrakovitz, G. David Poznik, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Alejandro Hernandez, Corinna Wong, Christophe Toukam Tchakouté, James MacKillop, David Stephens, Sarah L. Elson, Pierre Fontanillas, Jibran Y. Khokhar, Jared W. Young, Abraham A. Palmer

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueTranslational Psychiatry · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsWestern UniversityMcMaster UniversitySt. Joseph’s Healthcare HamiltonHomewood Research InstituteUniversity of Guelph
FundersNational Institute of Mental HealthVanderbilt University Medical CenterVanderbilt UniversityNational Institute on Drug AbuseTobacco-Related Disease Research ProgramNational Institute on Alcohol Abuse and AlcoholismBrain Research FoundationU.S. Department of Health and Human Services
KeywordsGenome-wide association studyPhenomeImpulsivityHeritabilityGenetic associationBig Five personality traitsBarratt Impulsiveness ScalePersonalityClinical psychologySingle-nucleotide polymorphismPsychologyGeneticsPsychiatryMedicineBiologyPhenotypeGeneGenotype

Abstract

fetched live from OpenAlex

Abstract Impulsivity is a multidimensional heritable phenotype that broadly refers to the tendency to act prematurely and is associated with multiple forms of psychopathology, including substance use disorders. We performed genome-wide association studies (GWAS) of eight impulsive personality traits from the Barratt Impulsiveness Scale and the short UPPS-P Impulsive Personality Scale ( N = 123,509–133,517 23andMe research participants of European ancestry), and a measure of Drug Experimentation ( N = 130,684). Because these GWAS implicated the gene CADM2 , we next performed single-SNP phenome-wide studies (PheWAS) of several of the implicated variants in CADM2 in a multi-ancestral 23andMe cohort ( N = 3,229,317, European; N = 579,623, Latin American; N = 199,663, African American). Finally, we produced Cadm2 mutant mice and used them to perform a Mouse-PheWAS (“MouseWAS”) by testing them with a battery of relevant behavioral tasks. In humans, impulsive personality traits showed modest chip-heritability (~6–11%), and moderate genetic correlations ( r g = 0.20–0.50) with other personality traits, and various psychiatric and medical traits. We identified significant associations proximal to genes such as TCF4 and PTPRF , and also identified nominal associations proximal to DRD2 and CRHR1 . PheWAS for CADM2 variants identified associations with 378 traits in European participants, and 47 traits in Latin American participants, replicating associations with risky behaviors, cognition and BMI, and revealing novel associations including allergies, anxiety, irritable bowel syndrome, and migraine. Our MouseWAS recapitulated some of the associations found in humans, including impulsivity, cognition, and BMI. Our results further delineate the role of CADM2 in impulsivity and numerous other psychiatric and somatic traits across ancestries and species.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation 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 score0.015
Threshold uncertainty score0.526

Codex and Gemma teacher scores by category

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

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 head0.023
GPT teacher head0.308
Teacher spread0.286 · 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