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Genetic underpinnings of sociability in the general population

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)...

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Autores principales: Bralten, Janita, Mota, Nina R., Klemann, Cornelius J. H. M., De Witte, Ward, Laing, Emma, Collier, David A., de Kluiver, Hilde, Bauduin, Stephanie E. E. C., Arango, Celso, Ayuso-Mateos, Jose L., Fabbri, Chiara, Kas, Martien J., van der Wee, Nic, Penninx, Brenda W. J. H., Serretti, Alessandro, Franke, Barbara, Poelmans, Geert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280100/
https://www.ncbi.nlm.nih.gov/pubmed/34054130
http://dx.doi.org/10.1038/s41386-021-01044-z
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author Bralten, Janita
Mota, Nina R.
Klemann, Cornelius J. H. M.
De Witte, Ward
Laing, Emma
Collier, David A.
de Kluiver, Hilde
Bauduin, Stephanie E. E. C.
Arango, Celso
Ayuso-Mateos, Jose L.
Fabbri, Chiara
Kas, Martien J.
van der Wee, Nic
Penninx, Brenda W. J. H.
Serretti, Alessandro
Franke, Barbara
Poelmans, Geert
author_facet Bralten, Janita
Mota, Nina R.
Klemann, Cornelius J. H. M.
De Witte, Ward
Laing, Emma
Collier, David A.
de Kluiver, Hilde
Bauduin, Stephanie E. E. C.
Arango, Celso
Ayuso-Mateos, Jose L.
Fabbri, Chiara
Kas, Martien J.
van der Wee, Nic
Penninx, Brenda W. J. H.
Serretti, Alessandro
Franke, Barbara
Poelmans, Geert
author_sort Bralten, Janita
collection PubMed
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. 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 h(2) 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.
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spelling pubmed-82801002021-07-19 Genetic underpinnings of sociability in the general population Bralten, Janita Mota, Nina R. Klemann, Cornelius J. H. M. De Witte, Ward Laing, Emma Collier, David A. de Kluiver, Hilde Bauduin, Stephanie E. E. C. Arango, Celso Ayuso-Mateos, Jose L. Fabbri, Chiara Kas, Martien J. van der Wee, Nic Penninx, Brenda W. J. H. Serretti, Alessandro Franke, Barbara Poelmans, Geert Neuropsychopharmacology Article 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 h(2) 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. Springer International Publishing 2021-05-30 2021-08 /pmc/articles/PMC8280100/ /pubmed/34054130 http://dx.doi.org/10.1038/s41386-021-01044-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bralten, Janita
Mota, Nina R.
Klemann, Cornelius J. H. M.
De Witte, Ward
Laing, Emma
Collier, David A.
de Kluiver, Hilde
Bauduin, Stephanie E. E. C.
Arango, Celso
Ayuso-Mateos, Jose L.
Fabbri, Chiara
Kas, Martien J.
van der Wee, Nic
Penninx, Brenda W. J. H.
Serretti, Alessandro
Franke, Barbara
Poelmans, Geert
Genetic underpinnings of sociability in the general population
title Genetic underpinnings of sociability in the general population
title_full Genetic underpinnings of sociability in the general population
title_fullStr Genetic underpinnings of sociability in the general population
title_full_unstemmed Genetic underpinnings of sociability in the general population
title_short Genetic underpinnings of sociability in the general population
title_sort genetic underpinnings of sociability in the general population
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280100/
https://www.ncbi.nlm.nih.gov/pubmed/34054130
http://dx.doi.org/10.1038/s41386-021-01044-z
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