Year: 2019
Type: preprint
Study design: Observational Study
Abstract: 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, p=6.6e-248) and ASDs (rg=0.27, p=4.5e-28), 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.
DOI: 10.1101/781195
Institutions: Radboud University Nijmegen, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, GGZ inGeest, University of Bologna, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Investigación Sanitaria Gregorio Marañón, University of Groningen, Leiden University Medical Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Fundación Alicia Koplowitz, European Federation of Pharmaceutical Industries and Associations, Ministerio de Ciencia, Innovación y Universidades, European Commission, Centro de Investigación Biomédica en Red de Salud Mental, Innovative Medicines Initiative, Horizon 2020 Framework Programme, Instituto de Salud Carlos III, European Regional Development Fund, FP7 Health
Awards: G1033681661, Biotipos en Trastornos del Espectro Autista: relación con evolución clínica y respuesta a fármacos, G1297764492, G1543110705, G1743590445, G1886919625, G2017605187, Estudio de vías fisiopatológicas diferenciales asociadas a fenotipos distintivos en una muestra de 200 pacientes con Trastornos del Espectro Autista, G2166927188, G2628364946, G3105035837, G3421866168, G3559709381, G3764841371, G3920792168, G434337789, G4345436876, G4637685055, Translating neuroimaging findings from research into clinical practice, G4937468798, G495187929, G5659272630, G5983053349, G60524263, G6081615879, G6446975009, Autism Innovative Medicine Studies – 2 – Trials, Envejecimiento celular asociado con exposición temprana a acontecimientos estresantes en el síndrome de deleción 22q11.2, Envejecimiento celular en primeros episodios psicóticos de inicio temprano, G7336256237, G7900017153, G8130688399, Psychiatric Ratings using Intermediate Stratified Markers - Sofia ref.: 115916, G8351277590, G8563726104, G85705433, G8824911526, G8950770007
OpenAlex ID: W2975120644