Polygenic scores differentially predict developmental trajectories of subtypes of social withdrawal in childhood

Abstract

Background: Children who consistently withdraw from social situations face increased risk for later socioemotional difficulties. Twin studies indicate that genetic factors substantially account for the persistence of social withdrawal over time. However, the molecular genetic etiology of chronic courses of social wariness and preference for solitude, two dimensions of social withdrawal, remains undocumented. The objectives of the present study were (a) to identify high-risk trajectories for social wariness and preference for solitude in childhood and (b) to examine whether falling on these high-risk trajectories can be predicted by specific polygenic scores for mental health traits and disorders and by a general polygenic predisposition to these traits. Methods: Teachers evaluated 971 genotyped children at five occasions (age 6 to 12 years) from two prospective longitudinal studies, the Quebec Newborn Twin Study and the Quebec Longitudinal Study of Child Development. Developmental trajectories for social wariness and preference for solitude were identified. We tested whether polygenic scores for attention deficit hyperactivity disorder, autism spectrum disorder, depression, loneliness, and subjective well-being, as well as a general mental health genetic risk score derived across these traits, were associated with the developmental trajectories. Results: Polygenic scores differentially predicted social wariness and preference for solitude. Only the loneliness polygenic score significantly predicted the high trajectory for social wariness. By contrast, the general mental health genetic risk score factor was associated with the trajectory depicting high-chronic preference for solitude. Conclusions: Distinct associations were uncovered between the polygenic scores, social wariness, and preference for solitude.

Early temperamental and biological predictors of dimensions of social withdrawal in childhood

“…Researchers have thus suggested that social avoidance may be an early marker of social anhedonia, a key symptom of depression. This proposition that social avoidance may carry a high psychopathological risk is further supported by recent genetic findings showing that, compared with socially wary children, those who prefer solitude are characterized by a higher polygenic risk for multiple mental health problems (e.g., depression, autism spectrum disorder, attention deficit/hyperactivity disorder; Morneau‐Vaillancourt et al., 2021). The present study therefore contributes to this emerging literature by suggesting that the combination of temperamental and biological vulnerabilities observed during the first years of life may be an early marker of psychopathological risk, which could in turn manifest behaviorally under the form of preference for solitude.…”

A Systematic Review and Meta-Analysis: Research Using the Autism Polygenic Score

“…Studies showed relatively large sample overlap: A total of 57 different samples were used across the 72 studies (pooled N = 720,087). The average percentage of males in the included study samples was 48.3% ( [25][26][27][28][29][30][31] ) omitted from this percentage due to missing or unclear sex information). Of the included studies 47.2% were performed on child or adolescent (<18 years) participants, 19.4% on adult (> 18 years) participants, 29.2% on a mixed sample of children and adults, and for 2,8% the sample age information was unavailable or unclear.…”

Adolescent anxiety and pain problems: A joint, genome-wide investigation and pathway-based analysis

“…Data was processed using Illumina's GenomeStudio platform, following the manufacturer's guidelines. All the collected samples passed a first round of QC [25]. In this first round, SNPs with call rates <98% or a minor allele frequency (MAF) <1% were removed as well as samples with <98% genotyping rate.…”