Genetic underpinnings of sociability in the UK Biobank

Abstract

Difficulties with sociability include a tendency to avoid social contacts and activities, and to prefer being alone rather than being with others. While sociability is a continuously distributed trait in the population, decreased sociability represent a common early manifestation of multiple neuropsychiatric disorders such as Schizophrenia (SCZ), Bipolar Disorder (BP), Major Depressive Disorder (MDD), Autism Spectrum Disorders (ASDs), and Alzheimer's disease (AD). We aimed to investigate the genetic underpinnings of sociability as a continuous trait in the general population. In this respect, we performed a genome-wide association study (GWAS) using a sociability score based on 4 social functioning-related self-report questions in the UK Biobank sample (n=342,461) to test the effect of individual genetic variants. This was followed by LD score analyses to investigate the genetic correlation with psychiatric disorders (SCZ, BP, MDD, ASDs) and a neurological disorder (AD) as well as related phenotypes (Loneliness and Social Anxiety). The phenotypic data indeed showed that the sociability score was decreased in individuals with ASD, (probable) MDD, BP and SCZ, but not in individuals with AD. Our GWAS showed 604 genome-wide significant SNPs, coming from 18 independent loci (SNP-based h2=0.06). Genetic correlation analyses showed significant correlations with SCZ (rg=0.15, p=9.8e-23), MDD (rg=0.68, and ASDs (rg=0.27,, but no correlation with BP (rg=0.01, p=0.45) or AD (rg=0.04, p=0.55). Our sociability trait was also genetically correlated with Loneliness (rg=0.45, p=2.4e-8) and Social Anxiety (rg=0.48, p=0.002). Our study shows that there is a significant genetic component to variation in population levels of sociability, which is relevant to some psychiatric disorders (SCZ, MDD, ASDs), but not to BP and AD.

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

“…These findings suggest a diverse genetic landscape of social phenotypes that is differentially shared with psychiatric disorder. As such, our results refine previous research demonstrating genetic overlap with psychiatric risk for social behaviourrelated traits such as emotion recognition in childhood and adolescence 31,32 , self-reported empathy 33 , loneliness 34 , and sociability 35 in adults.…”

“…The absence of genetic interrelationships with BP is consistent with previous reports 33,35,51 and either reflects lack of power or suggests that, genetically, social symptoms may not be directly involved in the genetic aetiology of the disorder.…”

Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): I. Psychosis superspectrum

“…Schizophrenia polygenic risk score was found to predict negative symptoms both in patients and in the general population 140‐143 . Also, anhedonia and low sociability demonstrated moderate genetic correlations with schizophrenia 144,145 .…”

Quantitative Genetic Scoring, or how to put a number on an arbitrary genetic region

“…A schematic overview of the genetic data sets and analyses can be found in Figure 1. The largest sample was the UK Biobank (UKBB) with the continuous psychiatric phenotype sociability (UKBB-s) (Bralten et al, 2019). The second largest sample was also from UKBB with the binary phenotype of lifetime cannabis use (UKBB-c) (Pasman et al, 2018).…”