Polygenic risk for psychiatric disorder reveals distinct association profiles across social behaviour in the general population

Abstract

Many complex psychiatric disorders are characterised by a spectrum of social difficulties. These symptoms lie on a behavioural dimension that is shared with social behaviour in the general population, with substantial contributions of genetic factors. However, shared genetic links may vary across psychiatric disorders and social symptoms. Here, we systematically investigate heterogeneity in shared genetic liabilities with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), bipolar disorder (BP), major depression (MD) and schizophrenia, across a spectrum of different social symptoms. Specifically, longitudinally assessed low-prosociality and peer-problem scores in two UK population-based/community-based cohorts (ALSPAC, N ≤ 6174, 4-17 years; TEDS, N ≤ 7112, 4-16 years; parent- and teacher-reports) were regressed on polygenic risk scores for ADHD, ASD, BP, MD, and schizophrenia, as informed by genome-wide summary statistics from large consortia, using negative binomial regression models. Across ALSPAC and TEDS, we replicated univariate polygenic associations between social behaviour and risk for ADHD, MD, and schizophrenia. Modelling univariate genetic effects across both cohorts with random-effect meta-regression revealed evidence for polygenic links between social behaviour and ADHD, ASD, MD, and schizophrenia risk, but not BP, where differences in age, reporter and social trait captured 45-88% in univariate effect variation. For ADHD, MD, and ASD polygenic risk, we identified stronger association with peer problems than low prosociality, while schizophrenia polygenic risk was solely associated with low prosociality. The identified association profiles suggest marked differences in the social genetic architecture underlying different psychiatric disorders when investigating population-based social symptoms across 13 years of child and adolescent development.

Research Review: A guide to computing and implementing polygenic scores in developmental research

“…However, the strength of association and the agerelated increases depended on the specific disorder considered. Similarly, Schlag et al (2021) found differential effects of PGS for psychiatric traits on social behavioural phenotypes (e.g. peer problems), as well as age-moderated effects, depending on the behavioural problem subtype considered.…”

“…Similarly, Schlag et al. (2021) found differential effects of PGS for psychiatric traits on social behavioural phenotypes (e.g. peer problems), as well as age‐moderated effects, depending on the behavioural problem subtype considered.…”

“…In practice, instead of creating one genome‐wide polygenic score for a particular trait, PRSset creates separate pathway‐PGS reflecting different biological processes or functions, which in turn can be employed for (disease) stratification and attempt to investigate biological relevance in complex traits. For example, schizophrenia‐based pathway‐PGS have been employed to uncover putative molecular mechanisms driving the association between schizophrenia polygenic risk and social behaviour in a child and adolescent sample (Schlag et al., 2021).…”