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Genetic underpinnings of sociability in the UK Biobank

J Bralten, CJHM Klemann, NR Mota, W De Witte, C Arango, C Fabbri, MJ Kas, N van der Wee, BWJH Penninx, A Serretti, B Franke, G Poelmans
doi: https://doi.org/10.1101/781195
J Bralten
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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  • For correspondence: janita.bralten@radboudumc.nl
CJHM Klemann
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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NR Mota
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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W De Witte
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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C Arango
2Institute of Psychiatry and Mental Health. Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), CIBERSAM, Madrid, Spain
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C Fabbri
3Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy
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MJ Kas
4Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands
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N van der Wee
5Department of Psychiatry, Leiden Institute for Brain and Cognition/Psychiatric Neuroimaging, Leiden University Medical Center, the Netherlands
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BWJH Penninx
6Department of Psychiatry, Amsterdam University Medical Center/GGZ in Geest, Amsterdam, The Netherlands
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A Serretti
3Department of Biomedical and NeuroMotor Sciences, University of Bologna, Italy
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B Franke
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
7Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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G Poelmans
1Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands
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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.

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Posted October 23, 2019.
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Genetic underpinnings of sociability in the UK Biobank
J Bralten, CJHM Klemann, NR Mota, W De Witte, C Arango, C Fabbri, MJ Kas, N van der Wee, BWJH Penninx, A Serretti, B Franke, G Poelmans
bioRxiv 781195; doi: https://doi.org/10.1101/781195
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Genetic underpinnings of sociability in the UK Biobank
J Bralten, CJHM Klemann, NR Mota, W De Witte, C Arango, C Fabbri, MJ Kas, N van der Wee, BWJH Penninx, A Serretti, B Franke, G Poelmans
bioRxiv 781195; doi: https://doi.org/10.1101/781195

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