{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T07:14:15Z","timestamp":1765178055351,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Brain and Behaviour Research Foundation","award":["(Independent Investigator Award 1930"],"award-info":[{"award-number":["(Independent Investigator Award 1930"]}]},{"name":"Lister Prize Fellowship","award":["173096"],"award-info":[{"award-number":["173096"]}]},{"name":"UKRI- HDR-UK Fellowship","award":["MR\/S003061\/1"],"award-info":[{"award-number":["MR\/S003061\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits. Methods: Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent. Results: Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus. Conclusions: Our systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.<\/jats:p>","DOI":"10.3390\/genes12081194","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"1194","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Genetic Variation in the ASTN2 Locus in Cardiovascular, Metabolic and Psychiatric Traits: Evidence for Pleiotropy Rather Than Shared Biology"],"prefix":"10.3390","volume":"12","author":[{"given":"Olivia","family":"Burt","sequence":"first","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keira J. A.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"},{"name":"Division of Psychiatry, University of Edinburgh, Edinburgh EH10 5HF, UK"},{"name":"School of Life Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Graham","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Breda","family":"Cullen","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Lyall","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M.","family":"Lyall","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill P.","family":"Pell","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joey","family":"Ward","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-3585","authenticated-orcid":false,"given":"Rona J.","family":"Strawbridge","sequence":"additional","affiliation":[{"name":"Institute of Health and Wellbeing, University of Glasgow, Glasgow G12 8QQ, UK"},{"name":"Health Data Research UK, Glasgow G12 8QQ, UK"},{"name":"Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, 17177 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/j.2051-5545.2011.tb00014.x","article-title":"Physical illness in patients with severe mental disorders. 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