Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

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

doi:10.1038/s41380-022-01793-3

Cited by 26 publications

(29 citation statements)

References 97 publications

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“…As a result, we included summary statistics from GWAS capturing a variety of parental risk factors for conduct problems in the domains of psychiatric conditions, substance use/abuse, cognitive and education-related factors, or other parental risk factors that could underlie potential genetic nurture effects (Table S2). Specifically, we used summary statistics for GWAS on ADHD (40), depression (41), anxiety disorders (42), antisocial behaviour (ASB) (43), lifetime smoking (44), problematic alcohol use (45), cannabis use disorder (CUD) (46), cognitive performance (47), educational attainment (47), household income (48), risky behaviours ( 49) and age at first birth (50).…”

Section: Selection Of Gwas Summary Statisticsmentioning

confidence: 99%

Examining Intergenerational Risk Factors for Conduct Problems Using Polygenic Scores in the Norwegian Mother, Father and Child Cohort Study

Frach¹,

Barkhuizen²,

Allegrini³

et al. 2023

Preprint

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Conduct problems in children and adolescents affect individuals, families, and their environment. The aetiology of conduct problems involves a combination of genetic and environmental risk factors, many of which are inherently linked to parental characteristics given parents’ central role in children’s lives across development. It is important to disentangle to what extent links between parental characteristics and children’s behaviour are due to transmission of genetic risk or due to environmentally mediated genetic influences on offspring behaviour (i.e., genetic nurture). We used 31,346 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 12 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Among genotyped trios, maternal reports of conduct problems at age 8 years were available for 15,516 children. We found significant genetic transmission effects on conduct problems for 11 out of 12 PGS (strongest positive association: PGS for smoking, β = 0.07 95% confidence interval = [0.05, 0.08]; strongest negative association: PGS for education, β = –0.04, 95% confidence interval = [¬–0.06, –0.02]). Conversely, we did not find strong evidence for genetic nurture effects for child conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics like psychiatric conditions or risk behaviours and child conduct problems. Our results may also indicate that genetic nurture is of limited aetiological importance for conduct problems—though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility.

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Section: Selection Of Gwas Summary Statisticsmentioning

confidence: 99%

Examining Intergenerational Risk Factors for Conduct Problems Using Polygenic Scores in the Norwegian Mother, Father and Child Cohort Study

Frach¹,

Barkhuizen²,

Allegrini³

et al. 2023

Preprint

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“…The presence of FOXP2 in the large introgression desert on chromosome 7 may have less to do with its well-known role in sensori-motor learning, and more to do with its associations with behavioral traits pertaining to sociability and externalizing behavior (Tielbeek et al, 2022 ; Verweij et al, 2022 ).…”

Section: Signals From Comparative (Paleo)genomicsmentioning

confidence: 99%

What made us “hunter-gatherers of words”

Boeckx

2023

Front. Neurosci.

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This paper makes three interconnected claims: (i) the “human condition” cannot be captured by evolutionary narratives that reduce it to a recent ‘cognitive modernity', nor by narratives that eliminates all cognitive differences between us and out closest extinct relatives, (ii) signals from paleogenomics, especially coming from deserts of introgression but also from signatures of positive selection, point to the importance of mutations that impact neurodevelopment, plausibly leading to temperamental differences, which may impact cultural evolutionary trajectories in specific ways, and (iii) these trajectories are expected to affect the language phenotypes, modifying what is being learned and how it is put to use. In particular, I hypothesize that these different trajectories influence the development of symbolic systems, the flexible ways in which symbols combine, and the size and configurations of the communities in which these systems are put to use.

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“…An extensive body of evidence points to this gene as a critical determinant of antisocial behavior 14 . In addition, a recent meta‐analysis based on genome‐wide association studies (GWAS) in antisocial individuals has shown a significant association between FOXP2 (transcription factor forkhead box protein P2) and antisocial behavior 15 …”

Section: Introductionmentioning

confidence: 99%

“…14 In addition, a recent meta-analysis based on genome-wide association studies (GWAS) in antisocial individuals has shown a significant association between FOXP2 (transcription factor forkhead box protein P2) and antisocial behavior. 15 Several lines of neuroimaging research have shown that the maladaptive social responses in antisocial behavior are contributed by structural and functional deficits of the orbitofrontal cortex (OFC) 16 (for scholarly discussions of the role of the OFC in antisocial behavior, see refs. [17,18]).…”

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confidence: 99%

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals

et al. 2023

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AimsAntisocial personality disorder (ASPD) and conduct disorder (CD) are characterized by a persistent pattern of violations of societal norms and others' rights. Ample evidence shows that the pathophysiology of these disorders is contributed by orbitofrontal cortex (OFC) alterations, yet the underlying molecular mechanisms remain elusive. To address this knowledge gap, we performed the first‐ever RNA sequencing study of postmortem OFC samples from subjects with a lifetime diagnosis of ASPD and/or CD.MethodsThe transcriptomic profiles of OFC samples from subjects with ASPD and/or CD were compared to those of unaffected age‐matched controls (n = 9/group).ResultsThe OFC of ASPD/CD‐affected subjects displayed significant differences in the expression of 328 genes. Further gene‐ontology analyses revealed an extensive downregulation of excitatory neuron transcripts and upregulation of astrocyte transcripts. These alterations were paralleled by significant modifications in synaptic regulation and glutamatergic neurotransmission pathways.ConclusionThese preliminary findings suggest that ASPD and CD feature a complex array of functional deficits in the pyramidal neurons and astrocytes of the OFC. In turn, these aberrances may contribute to the reduced OFC connectivity observed in antisocial subjects. Future analyses on larger cohorts are needed to validate these results.

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Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

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Cited by 26 publications

References 97 publications

Examining Intergenerational Risk Factors for Conduct Problems Using Polygenic Scores in the Norwegian Mother, Father and Child Cohort Study

Examining Intergenerational Risk Factors for Conduct Problems Using Polygenic Scores in the Norwegian Mother, Father and Child Cohort Study

What made us “hunter-gatherers of words”

A preliminary transcriptomic analysis of the orbitofrontal cortex of antisocial individuals

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