TY - JOUR
T1 - Genetic underpinnings of sociability in the general population
AU - Bralten, Janita
AU - Mota, Nina R.
AU - Klemann, Cornelius J. H. M.
AU - de Witte, Ward
AU - Laing, Emma
AU - Collier, David A.
AU - de Kluiver, Hilde
AU - Bauduin, Stephanie E. E. C.
AU - Arango, Celso
AU - Ayuso-Mateos, Jose L.
AU - Fabbri, Chiara
AU - Kas, Martien J.
AU - van der Wee, Nic
AU - Penninx, Brenda W. J. H.
AU - Serretti, Alessandro
AU - Franke, Barbara
AU - Poelmans, Geert
N1 - Funding Information: The PRISM project (www.prism-project.eu) leading to this work has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115916. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. This work reflects only the authors’ views, and neither IMI JU nor EFPIA nor the European Commission are liable for any use that may be made of the information contained therein. Further support was provided by the EU H2020 Program under the Innovative Medicines Initiative 2 Joint Undertaking with grant agreement 777394 (AIMS-2-TRIALS), the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III (PI14/00397, PI14/ 02103, PIE16/00055, PI17/00819, PI17/00481), co-financed by ERDF Funds from the European Commission, “A way of making Europe”, CIBERSAM, Madrid Regional Government (B2017/BMD-3740 AGES-CM-2), EU Structural Funds, EU Seventh Framework Program under grant agreement FP7-HEALTH-2013-2.2.1-2-603196 (Project PSYSCAN), Fundación Familia Alonso, Fundación Alicia Koplowitz. This work is also part of the research program Computing Time National Computing Facilities Processing Round pilots 2018 with project number 17666, which is (partly) financed by the Dutch Research Council (NWO). This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. NvdW received speaking bureau honoraria from Eli Lilly and Wyeth and served on advisory panels of Eli Lilly, Pfizer, Wyeth, and Servier. BP has received (non-related) research grants from Jansen research and Boehringer Ingelheim. AS is or has been consultant/speaker for: Abbott, Abbvie, Angelini, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lund-beck, Naurex, Pfizer, Polifarma, Sanofi, and Servier. BF has received educational speaking fees from Medice. GP is director of Drug Target ID, Ltd. The authors declare no competing interests. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85107381009&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41386-021-01044-z
DO - https://doi.org/10.1038/s41386-021-01044-z
M3 - Article
C2 - 34054130
SN - 0893-133X
VL - 46
SP - 1627
EP - 1634
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 9
ER -