Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior.
paper
Cited
Public
- Authors
- Tielbeek, Jorim J; Johansson, Ada; Polderman, Tinca J C; Rautiainen, Marja-Riitta; Jansen, Philip; Taylor, Michelle; Tong, Xiaoran; Lu, Qing; Burt, Alexandra S; Tiemeier, Henning; Viding, Essi; Plomin, Robert; Martin, Nicholas G; Heath, Andrew C; Madden, Pamela A F; Montgomery, Grant; Beaver, Kevin M; Waldman, Irwin; Gelernter, Joel; Kranzler, Henry R; Farrer, Lindsay A; Perry, John R B; MunafΓ², Marcus; LoParo, Devon; Paunio, Tiina; Tiihonen, Jari; Mous, Sabine E; Pappa, Irene; de Leeuw, Christiaan; Watanabe, Kyoko; Hammerschlag, Anke R; Salvatore, Jessica E; Aliev, Fazil; Bigdeli, Tim B; Dick, Danielle; Faraone, Stephen V; Popma, Arne; Medland, Sarah E; Posthuma, Danielle; Broad Antisocial Behavior Consortium collaborators
- Year
- 2017
- Journal
- JAMA psychiatry
- PMID
- 28979981
- DOI
- 10.1001/jamapsychiatry.2017.3069
- PMCID
- PMC6309228
IMPORTANCE: Antisocial behavior (ASB) places a large burden on perpetrators, survivors, and society. Twin studies indicate that half of the variation in this trait is genetic. Specific causal genetic variants have, however, not been identified. OBJECTIVES: To estimate the single-nucleotide polymorphism-based heritability of ASB; to identify novel genetic risk variants, genes, or biological pathways; to test for pleiotropic associations with other psychiatric traits; and to reevaluate the candidate gene era data through the Broad Antisocial Behavior Consortium. DESIGN, SETTING, AND PARTICIPANTS: Genome-wide association data from 5 large population-based cohorts and 3 target samples with genome-wide genotype and ASB data were used for meta-analysis from March 1, 2014, to May 1, 2016. All data sets used quantitative phenotypes, except for the Finnish Crime Study, which applied a case-control design (370 patients and 5850 control individuals). MAIN OUTCOME AND MEASURES: This study adopted relatively broad inclusion criteria to achieve a quantitative measure of ASB derived from multiple measures, maximizing the sample size over different age ranges. RESULTS: The discovery samples comprised 16β―400 individuals, whereas the target samples consisted of 9381 individuals (all individuals were of European descent), including child and adult samples (mean age range, 6.7-56.1 years). Three promising loci with sex-discordant associations were found (8535 female individuals, chromosome 1: rs2764450, chromosome 11: rs11215217; 7772 male individuals, chromosome X, rs41456347). Polygenic risk score analyses showed prognostication of antisocial phenotypes in an independent Finnish Crime Study (2536 male individuals and 3684 female individuals) and shared genetic origin with conduct problems in a population-based sample (394 male individuals and 431 female individuals) but not with conduct disorder in a substance-dependent sample (950 male individuals and 1386 female individuals) (R2β=β0.0017 in the most optimal model, Pβ=β0.03). Significant inverse genetic correlation of ASB with educational attainment (rβ=β-0.52, Pβ=β.005) was detected. CONCLUSIONS AND RELEVANCE: The Broad Antisocial Behavior Consortium entails the largest collaboration to date on the genetic architecture of ASB, and the first results suggest that ASB may be highly polygenic and has potential heterogeneous genetic effects across sex.
Miami Plot Showing P Values of the Single-Nucleotide Polymorphism Associations With Antisocial Behavior in Males and FemalesThe threshold for genome-wide significance (P < 1.67 Γ 10β8) is indicated by the red dotted line, and the threshold for promising findings(P < 1.0 Γ 10β5) is indicated by the blue dotted line.
Polygenic Risk Scores (PRSs) in the Finnish Crime Study, Michigan State University Twin Registry (MSUTR), and Yale-Penn Samples.The PRSs for antisocial personality disorder (ASPD) among patients with antisocial behavior (ASB) in the Finnish Crime Study using sex-combined (A) and male-only (B) samples. Summary-summary statisticβbased results plotting the explained variance in ASB within the MSUTR (sex combined [C], males only [D], and females only [E]) and Yale-Penn (sex combined [F], males only [G], and females only [H]) samples. The proportion of variance explained (Nagelkerke R2) was computed by comparison of a full model (covariates plus PRS) score with a reduced model (covariates only). Seven different P value thresholds for selecting risk alleles are denoted by the color of each bar. The number of single-nucleotide polymorphisms (SNPs) per threshold is displayed below each bar. a Statistical significance at P < .05. b Statistical significance after correcting for multiple testing at P < .006.
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Next β
| Name | Type |
|---|---|
| ADHD | phenotype |
| adoption studies | cohort |
| Adult antisocial behaviour local | phenotype |
| age at first birth | phenotype |
| age at menarche | phenotype |
| age at menopause | phenotype |
| aggression | phenotype |
| American adults | cohort |
| antisocial personality disorder | phenotype |
| antisocial phenotypes local | phenotype |
| Antisocial phenotypes local | phenotype |
| ASB | phenotype |
| attention deficit hyperactivity disorder | phenotype |
| Behavioural disinhibition | phenotype |
| bipolar disorder | phenotype |
| BMI | phenotype |
| BroadABC local | cohort |
| BroadABC antisocial genetic risk scores local | drug |
| Broad Antisocial Behaviour Consortium local | cohort |
| catecholamines | drug |
| CENPI local | gene |
| Center on Antisocial Drug Dependence | cohort |
| childhood conduct disorder | phenotype |
| cognitive traits | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| conduct disorder | phenotype |
| crime | phenotype |
| deceitfulness | phenotype |
| depressive symptoms | phenotype |
| discovery sample | cohort |
| Drug and alcohol abuse local | phenotype |
| educational attainment | phenotype |
| Emotion | phenotype |
| European ancestry | cohort |
| externalizing disorders | phenotype |
| Female meta-analysis local | cohort |
| Females meta-analysis (N=8535) local | cohort |
| Finnish Crime Study local | cohort |
| Forensic cohort local | cohort |
| Forensic Sample local | cohort |
| genetic variants | cohort |
| height | phenotype |
| hostility | phenotype |
| LDHUB local | cohort |
| Maladaptive behaviours local | phenotype |
| male-female GWAS results local | phenotype |
| Male meta-analysis local | cohort |
| Males meta-analysis (N=7772) local | cohort |
| meta-analysis | cohort |
| MSUTR local | cohort |
| neuroticism | phenotype |
| number of children ever born | phenotype |
| Polygenic risk local | variant |
| polygenic risk score | cohort |
| Population-based discovery cohorts local | cohort |
| population-based sample | cohort |
| Post-Traumatic Stress Disorder | phenotype |
| poverty | phenotype |
| Psychiatric Genomics Consortium | cohort |
| psychiatric traits | phenotype |
| Psychopathic tendencies local | phenotype |
| QIMR | cohort |
| reproductive traits | phenotype |
| rs11215217 | variant |
| rs2764450 | variant |
| rs41456347 local | variant |
| samples | cohort |
| schizophrenia | phenotype |
| serotonin | drug |
| sex | phenotype |
| SNP | cohort |
| Social pathologies local | phenotype |
| Social Science Genetic Association Consortium | cohort |
| Substance-Dependent Sample local | cohort |
| TEDS | cohort |
| Th | gene |
| Theft | phenotype |
| Twin cohort | cohort |
| unemployment | phenotype |
| Violent criminal behaviour local | phenotype |
| Violent felonies local | phenotype |
| Yale-Penn | cohort |
| YalePenn | cohort |
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