| Application: | 30619, Genetic underpinnings of social withdrawal in the general population |
| Title: | Genetic underpinnings of sociability in the general population |
| Size: | 502234 B |
| Cost Tier: | 1 |
| Archived: | 2 Nov 2021 |
| Stability: | Complete |
| Personal: | No individual-level data |
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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. We performed a genome-wide association study (GWAS) of a sociability score based on four social functioning-related self-report questions from 342,461 adults in the UK Biobank. Subsequently we performed gene-wide and functional follow-up analyses. Robustness analyses were performed in the form of GWAS split-half validation analyses, as well as analyses excluding neuropsychiatric cases. Using genetic correlation analyses as well as polygenic risk score analyses we investigated genetic links of our sociability score to brain disorders and social behavior outcomes. Individuals with autism spectrum disorders, bipolar disorder, depression, and schizophrenia had a lower sociability score. The score was significantly heritable (SNP h2 of 6%). We identified 18 independent loci and 56 gene-wide significant genes, including genes like ARNTL, DRD2, and ELAVL2. Many associated variants are thought to have deleterious effects on gene products and our results were robust. The sociability score showed negative genetic correlations with autism spectrum, disorders, depression, schizophrenia, and two sociability-related traits-loneliness and social anxiety-but not with bipolar disorder or Alzheimer's disease. Polygenic risk scores of our sociability GWAS were associated with social behavior outcomes within individuals with bipolar disorder and with major depressive disorder. Variation in population sociability scores has a genetic component, which is relevant to several psychiatric disorders. Our findings provide clues towards biological pathways underlying sociability.Application 30619
Genetic underpinnings of social withdrawal in the general population
Social withdrawal is present as a trait in the general population and is a common early symptom of multiple neurological diseases, including schizophrenia, Alzheimer?s disease, and major depressive disorder. However, the underlying, biological causes of social withdrawal (either as a trait or a disease state) are still poorly understood and may also differ between diseases. Within the PRISM project (www.prism-project.eu), we aim to elucidate the genetics, and as such the biological etiology, of social withdrawal within the general population as well as patients with schizophrenia, Alzheimer?s disease, and major depressive disorder. The proposed research aims to shed new light on the biological underpinnings of social withdrawal, in terms of its genetics as well as its link to cognitive function and disease. This knowledge can contribute on the longer term to the prevention, diagnosis, and treatment of social withdrawal in various brain disorders, including schizophrenia, Alzheimer?s disease, and major depressive disorder. We aim to identify the genetic underpinnings of social withdrawal. We will use a hypothesis-free approach, i.e. we will conduct a genome-wide association study (GWAS) to test the association between ~13 million common single nucleotide variants (i.e. SNPs) and a 'social withdrawal score' generated from answers to the questions about participation in social activities assessed in the UK Biobank participants. In this way, we will zoom in on the genetic variants that are most strongly linked to social withdrawal, which we can use to deduce the biological processes involved in social withdrawal. Due to the expected small effect sizes of individual common genetic variants involved in social withdrawal, we would like to include the full cohort (approximately 500.000 participants), i.e. the genome-wide genotyping data of all participants that answered the questions in data-field 1031 (frequency of friend/family visits) and/or data-field 6160 (leisure/social activities), data-field 1110 and 1120 (mobile phone use).
| Lead investigator: | Professor Barbara Franke |
| Lead institution: | Radboud University Medical Centre |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 4945 | Genetic underpinnings of sociability in the general population | Janita Bralten (+16) | 2021 | Neuropsychopharmacology |
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