{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:24:47Z","timestamp":1783488287970,"version":"3.55.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,12]]},"abstract":"\nObjective<\/jats:title>\nThyrotoxic periodic paralysis (TPP) is a rare and potentially fatal complication of hyperthyroidism. By meta-analysis of genome-wide association studies, we aim to discover novel susceptibility loci and understand the pathogenesis of TPP.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nThis meta-analysis comprised 319 TPP cases and 3516 healthy controls from three independent cohorts (two from Hong Kong; one from Shanghai). Genetic variants in each cohort were separately genotyped, imputed and analyzed for association with TPP. Fixed-effect meta-analysis was performed to combine the data. Using the three independent genome-wide significant variants, a weighted genetic risk score (GRS) was developed.<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nOf 7 077 246 variants tested for association with TPP, 260 variants reached genome-wide significance and were represented by independent variants from four distinct genomic loci, but a risk locus for Graves\u2019 disease at 6p21.33\u2013p21.22 was excluded from subsequent analyses. Two novel loci near TRIM2<\/jats:italic> (4q31.3; rs6827197: OR\u2009=\u20094.075; P<\/jats:italic> = 3.46 \u00d7 10\u22129<\/jats:sup>) and AC140912.1<\/jats:italic> (16q22.3; rs6420387: OR\u2009=\u20091.861; P<\/jats:italic> = 2.66 \u00d7 10\u22128<\/jats:sup>) were identified. Together with previously reported KCNJ2<\/jats:italic> (17q24.3; rs312743: OR\u2009=\u20092.564; P<\/jats:italic>\u2009=\u20091.15 \u00d7 10\u221221<\/jats:sup>), the three susceptibility variants explained 4.36% of the genetic liability. Expression quantitative trait loci analyses showed the variants altered expression of TRIM2<\/jats:italic> in nerve and KCNJ2<\/jats:italic> in skeletal muscle. The weighted GRS had an area under curve of 0.827 and 0.682 in the derivation and validation cohorts in Hong Kong.<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nWe identified two novel TPP risk loci near TRIM2<\/jats:italic> and AC140912.1<\/jats:italic>. While rare mutations in TRIM2<\/jats:italic> and KCNJ2<\/jats:italic> were implicated in monogenic disorders characterized by muscle paralysis, our study suggested common variants near these genes might dysregulate gene expression and lead to milder phenotypes.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0523","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T15:30:53Z","timestamp":1601307053000},"page":"607-617","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":3,"title":["Genome-wide meta-analysis reveals novel susceptibility loci for thyrotoxic periodic paralysis"],"prefix":"10.1093","volume":"183","author":[{"given":"Gloria","family":"Hoi-Yee Li","sequence":"first","affiliation":[{"name":"1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong"},{"name":"2Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Lung","family":"Cheung","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang-Xia","family":"Zhao","sequence":"additional","affiliation":[{"name":"3Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-dong","family":"Song","sequence":"additional","affiliation":[{"name":"3Department of Molecular Diagnostics, The Core Laboratory in Medical Center of Clinical Research, Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiaotong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Wai-Chee Kung","sequence":"additional","affiliation":[{"name":"4Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/6\/EJE-20-0523.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/6\/EJE-20-0523.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:15:09Z","timestamp":1676391309000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/6\/607\/6653876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0523","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12]]}}}