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Record W3208273675 · doi:10.1101/2021.10.19.462578

Uncovering the Genetic Architecture of Broad Antisocial Behavior through a Genome-Wide Association Study Meta-analysis

2021· preprint· en· W3208273675 on OpenAlexaff
Jorim J. Tielbeek, Emil Uffelmann, Benjamin Williams, Lucía Colodro‐Conde, Éloi Gagnon, Travis T. Mallard, Brandt Levitt, Philip R. Jansen, A Johansson, Hannah Sallis, Giorgio Pistis, Gretchen Saunders, Andrea G. Allegrini, Kaili Rimfeld, Bettina Konte, Marieke Klein, Annette M. Hartmann, Jessica E. Salvatore, Ilja M. Nolte, Ditte Demontis, Anni Malmberg, S. Alexandra Burt, Jeanne E. Savage, Karen Sugden, Richie Poulton, Kathleen Mullan Harris, Scott Vrieze, Matt McGue, William G. Iacono, Nina Roth Mota, Jonathan Mill, Joana Viana, Brittany L. Mitchell, José J. Morosoli, Till F. M. Andlauer, Isabelle Ouellet‐Morin, Richard E. Tremblay, Sylvana M. Côté, Jean‐Philippe Gouin, Mara Brendgen, Ginette Dionne, Frank Vitaro, Michelle K. Lupton, Nicholas G. Martin, Enrique Castelao, Katri Räikkönen, Johan G. Eriksson, Jari Lahti, Catharina A. Hartman, Albertine J. Oldehinkel, Harold Snieder, Hexuan Liu, Martin Preisig, Alyce M. Whipp, Eero Vuoksimaa, Yi Lu, Patrick Jern, Dan Rujescu, Ina Giegling, Teemu Palviainen, Jaakko Kaprio, K. Paige Harden, Marcus R. Munafò, Geneviève Morneau‐Vaillancourt, Robert Plomin, Essi Viding, Brian B. Boutwell, Fazil Alıev, Danielle M. Dick, Arne Popma, Stephen V. Faraone, Anders D. Børglum, Sarah E. Medland, Barbara Franke, Michel Boivin, Jean‐Baptiste Pingault, Jeffrey Glennon, J. C. Barnes, Simon E. Fisher, Terrie E. Moffitt, Avshalom Caspi, Tinca J. C. Polderman, Daniëlle Posthuma

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Mapping and Diversity in Plants and Animals
Canadian institutionsUniversité du Québec à MontréalUniversité de MontréalUniversité Laval
Fundersnot available
KeywordsGenetic architectureHeritabilityGenome-wide association studySNPGeneticsAggressionPsychopathyPleiotropyAntisocial personality disorderMeta-analysisTraitBiologyMissing heritability problemGenotypeGenetic correlationGenetic associationQuantitative trait locusPsychologyGenetic variationSingle-nucleotide polymorphismDevelopmental psychologyGenePoison controlMedicineInjury preventionInternal medicinePhenotypePersonality

Abstract

fetched live from OpenAlex

Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery samples (N = 85,359) and five independent replication samples (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10-10). Furthermore, we observed intronic variation in Foxp2 and one of its targets (Cntnap2) distinguishing a mouse model of pathological aggression (BALB/cJ strain) from controls (BALB/cByJ strain). Polygenic risk score (PRS) analyses in independent samples revealed that the genetic risk for ASB was associated with several antisocial outcomes across the lifespan, including diagnosis of conduct disorder, official criminal convictions, and trajectories of antisocial development. We found substantial genetic correlations of ASB with mental health (depression rg = 0.63, insomnia rg = 0.47), physical health (overweight rg = 0.19, waist-to-hip ratio rg = 0.32), smoking (rg = 0.54), cognitive ability (intelligence rg = -0.40), educational attainment (years of schooling rg = -0.46) and reproductive traits (age at first birth rg = -0.58, father's age at death rg = -0.54). Our findings provide a starting point toward identifying critical biosocial risk mechanisms for the development of ASB.

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)0.010
metaresearch head score (Gemma)0.011
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Meta-analysis · Consensus signal: Meta-analysis
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.010
Threshold uncertainty score0.051

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0100.011
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0050.018
Bibliometrics0.0040.006
Science and technology studies0.0010.001
Scholarly communication0.0030.001
Open science0.0010.002
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

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 head0.022
GPT teacher head0.235
Teacher spread0.214 · 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 designMeta-analysis
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

Citations8
Published2021
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)Same topicGenetic Mapping and Diversity in Plants and AnimalsFrench-language works237,207