DOI: 10.17026/dans-ztj-zga6
title: Sociability GWAS in a population-based sample

description: Levels of sociability are continuously distributed in the general population, and decreased sociability represents an early manifestation of several brain disorders. Here, we investigated the genetic underpinnings of sociability in the population.Main question of our research: 1. Are there common genetic variants that are associated with sociability in the general population? 2. Are genetic variants that are associated with sociability also associated with neuropsychiatric disorders?Type of data uploaded in this repository:The UK Biobank project (see https://www.ukbiobank.ac.uk/) is a large-scale biomedical database and research resource, containing in-depth genetic and health information from half a million UK participants. The database is globally accessible to approved researchers undertaking vital research into the most common and life-threatening diseases. The raw data that this project is based on comes from the publically available UK Biobank set, which is very large and is therefore not provided here. Here we only provide the results from our analysis, that is also described here: https://www.biorxiv.org/content/10.1101/781195v2 and currently in revision in a scientific journal. In the dataset you will find the association of 9327396 genetic variants with the phenotype sociability. This dataset is not applicable to be opened with Excel, and can best be opened on a cluster computer or using specfic software.SubjectsThe UK Biobank (UKBB) is a major population-based cohort from the United Kingdom that includes individuals aged between 37 and 73 years. We constructed a sociability measure based on the the aggregation of scores per participant on four questions from the UKBB database that link to sociability, including (1) a question about the frequency of friend/family visits, (2) a question on the number and type of social venues that are visited, (3) a question about worrying after social embarrassment and (4) a question about feeling lonely, leading to a sociability score ranging from 0-4. Participants were excluded if they had somatic problems that could be related to social withdrawal (BMI &lt; 15 or BMI &gt; 40, narcolepsy (all the time), stroke, severe tinnitus, deafness or brain-related cancers) or if they answered that they had “No friends/family outside household” or “Do not know” or “Prefer not to answer” to any of the questions.SNP genotyping and quality controlDetails about the available genome-wide genotyping data for UKBB participants have been reported previously (PMID: 30305743). We used third-release genotyping data (see https://biobank.ctsu.ox.ac.uk/crystal/label.cgi?id=100319). Briefly, 49,950 participants were genotyped using the UK BiLEVE Axiom Array and 438,427 participants were genotyped using UK Biobank Axiom Array. Genotypes were imputed into the dataset using the Haplotype Reference Consortium (HRC), and the UK10K haplotype resource. To account for ethnicity, we included only those individuals that identified themselves as "white" by self-report and plotted the Principal Components (PC) provided by the UKBB, excluding individuals considered to be outliers according to PCs 1 and 2. Genetic relatedness calculated with KING kinship and provided by the UKBB (https://kenhanscombe.github.io/ukbtools/articles/explore-ukb-data.html ; http://www.ukbiobank.ac.uk/wp-content/uploads/2014/04/UKBiobank_genotyping_QC_documentation-web.pdf) was used to identify first and second-degree relatives. Subsequently ´families´ (i.e. clusters of related individuals above an IBD&gt;0.125 threshold) were created and only one individual from each of these created ‘families’ was included in the analysis. If self-reported sex and SNP-based sex differed, individuals were excluded from further analysis. Single nucleotide polymorphisms (SNPs) with minor allele frequency &lt;0.005, Hardy-Weinberg equilibrium test P value&lt;1e−6, missing genotype rate &gt;0.05, and imputation quality of INFO &lt;0.8 were excluded. In the current study, all analyses are based on 342,461 participants of European ancestry for which both genotype data and sociability scores were available.Genome-wide association analysisGenome-wide association analysis with the imputed marker dosages was performed in PLINK1.9, using a linear regression model with the sociability measure as the dependent variable and including sex, age, 10 first PCs, assessment center, and genotype batch as covariates. SNPs were considered significantly associated if they had p-value &lt; 5e-8. Associated loci were considered independent of each other at r2 0.6 and lead SNPs were classified as the SNP with the smallest association p-value and at r2 0.1, using a 250kb window.The summary statistics come from the plink2 linear regression analysis.