{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T14:07:29Z","timestamp":1774102049646,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,11,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Genetic factors underpin the narrow intraindividual variability of thyroid function, although precise contributions of environmental vs genetic factors remain uncertain. We sought to clarify the heritability of thyroid function traits and thyroid peroxidase antibody (TPOAb) positivity and identify single nucleotide polymorphisms (SNPs) contributing to the trait variance.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Heritability of thyroid-stimulating hormone (TSH), free T4 (fT4), free T3 (fT3) and TPOAb in a cohort of 2854 euthyroid, dizygous and monozygous twins (age range 11.9\u201316.9 years) from the Brisbane Longitudinal Twin Study (BLTS) was assessed using structural equation modelling. A genome-wide analysis was conducted on 2832 of these individuals across 7 522 526 SNPs as well as gene-based association analyses. Replication analysis of the association results was performed in the Raine Study (<jats:italic>n<\/jats:italic>\u2009=\u20091115) followed by meta-analysis to maximise power for discovery.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Heritability of thyroid function parameters in the BLTS was 70.8% (95% CI: 66.7\u201374.9%) for TSH, 67.5% (59.8\u201375.3%) for fT4, 59.7% (54.4\u201365.0%) for fT3 and 48.8% (40.6\u201356.9%) for TPOAb. The genome-wide association study (GWAS) in the discovery cohort identified a novel association between rs2026401 upstream of <jats:italic>NCOA3<\/jats:italic> and TPOAb. GWAS meta-analysis found associations between TPOAb and rs445219, also near <jats:italic>NCOA3<\/jats:italic>, and fT3 and rs12687280 near <jats:italic>SERPINA7<\/jats:italic>. Gene-based association analysis highlighted <jats:italic>SERPINA7<\/jats:italic> for fT3 and <jats:italic>NPAS3<\/jats:italic> for fT4.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our findings resolve former contention regarding heritability estimates of thyroid function traits and TPOAb positivity. GWAS and gene-based association analysis identified variants accounting for a component of this heritability.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0614","type":"journal-article","created":{"date-parts":[[2021,9,15]],"date-time":"2021-09-15T16:05:53Z","timestamp":1631721953000},"page":"743-753","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":8,"title":["Genome-wide analysis of thyroid function in Australian adolescents highlights SERPINA7 and NCOA3"],"prefix":"10.1093","volume":"185","author":[{"given":"James","family":"Nolan","sequence":"first","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Purdey J","family":"Campbell","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne J","family":"Brown","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gu","family":"Zhu","sequence":"additional","affiliation":[{"name":"2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Gordon","sequence":"additional","affiliation":[{"name":"2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ee Mun","family":"Lim","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"},{"name":"3Pathwest Laboratory Medicine, Nedlands, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Joseph","sequence":"additional","affiliation":[{"name":"3Pathwest Laboratory Medicine, Nedlands, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone M","family":"Cross","sequence":"additional","affiliation":[{"name":"2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay","family":"Panicker","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"},{"name":"5Medical School, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E","family":"Medland","sequence":"additional","affiliation":[{"name":"2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip E","family":"Melton","sequence":"additional","affiliation":[{"name":"4School of Biomedical Sciences, Curtin University, Bentley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence J","family":"Beilin","sequence":"additional","affiliation":[{"name":"5Medical School, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor A","family":"Mori","sequence":"additional","affiliation":[{"name":"5Medical School, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin H","family":"Mullin","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"},{"name":"8School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig E","family":"Pennell","sequence":"additional","affiliation":[{"name":"6School of Medical and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carol A","family":"Wang","sequence":"additional","affiliation":[{"name":"6School of Medical and Public Health, University of Newcastle, Callaghan, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Dudbridge","sequence":"additional","affiliation":[{"name":"7Department of Health Sciences, University of Leicester, Leicester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P","family":"Walsh","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"},{"name":"5Medical School, University of Western Australia, Crawley, Western Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas G","family":"Martin","sequence":"additional","affiliation":[{"name":"2QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott G","family":"Wilson","sequence":"additional","affiliation":[{"name":"1Department of Endocrinology & Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia"},{"name":"8School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia, Australia"},{"name":"9Department of Twin Research & Genetic Epidemiology, King\u2019s College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["European Journal of 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