Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

Tielbeek, Jorim J.; Johansson, Ada; Polderman, Tinca J. C.; Rautiainen, Marja-Riitta; Jansen, Philip R.; Taylor, Michelle; Tong, Xiaoran; Lu, Qing; Burt, Alexandra; Tiemeier, Henning; Viding, Essi; Plomin, Robert; Martin, Nicholas G.; Heath, Andrew C.; Madden, Pamela A. F.; Montgomery, Grant W.; Beaver, Kevin M.; Waldman, Irwin D.; Gelernter, Joel; Kranzler, Henry R.; Farrer, Lindsay A.; Perry, John R. B.; Munafò, Marcus R.; LoParo, Devon; Paunio, Tiina; Tiihonen, Jari; Mous, Sabine E.; Pappa, Irene; Leeuw, Christiaan de; Watanabe, Kyoko; Hammerschlag, Anke R.; Salvatore, Jessica E.; Alıev, Fazil; Bigdeli, Tim B.; Dick, Danielle M.; Faraone, Stephen V.; Popma, Arne; Medland, Sarah E.; Posthuma, Daniëlle

doi:10.1001/jamapsychiatry.2017.3069

Cited by 192 publications

(147 citation statements)

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“…This latter idea is supported by epidemiological studies linking aggression to decreased educational attainment [59][60][61] . Finally, we found a significantly higher load of variants associated with younger age at birth of first child in ADHD+DBDs compared to ADHD without DBDs, in line with the observed positive genetic correlations of ADHD and anti-social behavior with having children earlier 29,41 and with evolutionary theories suggesting that aggression has played a role when competing for access to mates 62 .…”

Section: Discussionsupporting

confidence: 86%

“…This idea is supported by our finding of increased PRS for aggression in ADHD+DBDs compared to ADHD without DBDs (Supplementary Figure 7B). This conclusion is reinforced by the genetic correlation results, where we found somewhat higher genetic correlation of ADHD+DBDs with both aggressive behavior in children 28 and antisocial behavior 29 ( Supplementary Table 7) compared to those found for ADHD without DBDs.…”

Section: Discussionsupporting

confidence: 59%

“…This could reflect the increased genetic load of ADHD risk variants in ADHD+DBDs, since ADHD has a strong negative genetic correlation with cognitionrelated phenotypes 42 . However, it might also involve variants associated with anti-social behavior, which also has a negative genetic correlation with educational performance 30 . This latter idea is supported by epidemiological studies linking aggression to decreased educational attainment [61][62][63] .…”

Section: Discussionmentioning

confidence: 99%

“…Several genome-wide association studies (GWASs) have focused on diagnosed DBDs 27,28 or aggressive and anti-social behaviors 29,30 , with only limited success in identifying genome-wide significant loci and no conclusive, replicated findings 27,29,30 . Only two genome-wide studies have focused specifically on ADHD+DBDs.…”

Section: Introductionmentioning

confidence: 99%

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Identification of risk variants and characterization of the polygenic architecture of disruptive behavior disorders in the context of ADHD

Demontis

Walters

Rajagopal

et al. 2019

Preprint

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Attention-Deficit/Hyperactivity Disorder (ADHD) is a childhood psychiatric disorder often comorbid with disruptive behavior disorders (DBDs). ADHD comorbid with DBDs (ADHD+DBDs) is a complex phenotype with a risk component that can be attributed to common genetic variants. Here we report a large GWAS meta-analysis of ADHD+DBDs based on seven cohorts in total including 3,802 cases and 31,305 controls. Three genome-wide significant loci were identified on chromosomes 1, 7, and 11. A GWAS meta-analysis including a Chinese cohort supported the locus on chromosome 11 to be a strong risk locus for ADHD+DBDs across European and Chinese ancestries (rs7118422, P=3.15x10 -10 , OR=1.17). This locus was not associated with ADHD without DBDs in a secondary GWAS of 13,583 ADHD cases and 22,314 controls, suggesting that the locus is a specific risk locus for the comorbid phenotype.We found a higher SNP heritability for ADHD+DBDs (h 2 SNP =0.34) when compared to ADHD without DBDs (h 2 SNP =0.20). Genetic correlations of ADHD+DBDs with aggressive (r g =0.81) and anti-social behaviors (r g =0.82) were high, and polygenic risk score analyses revealed a significant increased burden of variants associated with ADHD and aggression in individuals with ADHD+DBDs compared to ADHD without DBDs. Our results suggests that ADHD+DBDs represent a more severe phenotype with respect to the genetic risk load than ADHD without DBDs, in line with previous studies, and that the risk load to some extent can be explained by variants associated with aggressive behavior.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of risk variants and characterization of the polygenic architecture of disruptive behavior disorders in the context of ADHD

Demontis

Walters

Rajagopal

et al. 2019

Preprint

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“…The educational-attainment polygenic scores’ prediction of offending careers was mediated by primary-school risk factors: lower cognitive abilities, lower self-control, academic difficulties, and truancy. Soon polygenic scores for conviction itself will be derived from GWAS 56 , which can be tested for LCP-specific risk.…”

Section: Predictions From the 1993 Taxonomy; How Have They Fared?mentioning

confidence: 99%

Male antisocial behaviour in adolescence and beyond

2018

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Male antisocial behavior is concentrated in the adolescent period of the life course, as documented by the curve of crime over age. This article reviews recent evidence regarding the hypothesis that the age-crime curve conceals two groups with different causes. Life-course persistent males show extreme, pervasive, persistent antisocial behavior from early childhood to adulthood. They are hypothesized to be rare, with pathological risk factors and poor life outcomes. In contrast, adolescence-limited males show similar levels of antisocial behavior but primarily during the adolescent stage of development. They are hypothesized to be common and normative, whereas abstainers from offending are rare. This article recaps the taxonomy’s 25-year history, concluding that it is standing the test of time in research, and making an impact on policy in early-years prevention and juvenile justice. Research is needed into how the taxonomy relates to neuroscience, health, genetics, and changes in modern crime, including digital crime.

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Incorrect Degree in Byline

2018

JAMA Psychiatry

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Incorrect Wave 4 ReportingTo the Editor We have discovered an error in our questionnaire underlying the analyses of the article titled "Accuracy of Reports of Lifetime Mental and Physical Disorders: Results From the Baltimore Epidemiological Catchment Area Study." 1 The error was discovered internally in the process of reviewing the questionnaire for each wave. We found that the wave 4 lifetime diagnoses for obsessive-compulsive disorder, panic disorder, social phobia, and alcohol use disorder were based on reports of these disorders since wave 3 and not the whole lifetime. This has likely led to some underreporting of lifetime disorders at wave 4. However, the substantive results of the study are valid because the cumulative lifetime prevalence estimates at wave 3 for most of these disorders were significantly larger than the prevalence estimates based on wave 3 lifetime reports alone. The wave 4 lifetime diagnoses for other disorders covered the whole lifetime.The primary data for all waves, the data analysis, and the data presented throughout the article were reviewed but remained unaltered. The article was corrected to clarify this error. 2

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Genome-Wide Association Studies of a Broad Spectrum of Antisocial Behavior

Abstract: 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.

Cited by 192 publications

References 50 publications

Identification of risk variants and characterization of the polygenic architecture of disruptive behavior disorders in the context of ADHD

Identification of risk variants and characterization of the polygenic architecture of disruptive behavior disorders in the context of ADHD

Male antisocial behaviour in adolescence and beyond

Incorrect Degree in Byline

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