{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:25:49Z","timestamp":1793157949783,"version":"4.5.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T00:00:00Z","timestamp":1436227200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T00:00:00Z","timestamp":1436227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Graves\u2019 disease is the leading cause of hyperthyroidism affecting 1.0\u20131.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves\u2019 disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate\n                    <jats:italic>HLA-B*38:02<\/jats:italic>\n                    (Armitage trend\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>combined<\/jats:sub>\n                    =6.75 \u00d7 10\n                    <jats:sup>\u221232<\/jats:sup>\n                    ) and\n                    <jats:italic>HLA-DRB1*08:03<\/jats:italic>\n                    (\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>combined<\/jats:sub>\n                    =1.83 \u00d7 10\n                    <jats:sup>\u22129<\/jats:sup>\n                    ) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13\u201341.48) and 6.13 (95% confidence interval=3.28\u201311.46), respectively. Carrying both\n                    <jats:italic>HLA-B*38:02<\/jats:italic>\n                    and\n                    <jats:italic>HLA-DRB1*08:03<\/jats:italic>\n                    increases odds ratio to 48.41 (\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>combined<\/jats:sub>\n                    =3.32 \u00d7 10\n                    <jats:sup>\u221221<\/jats:sup>\n                    , 95% confidence interval=21.66\u2013108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.\n                  <\/jats:p>","DOI":"10.1038\/ncomms8633","type":"journal-article","created":{"date-parts":[[2015,7,7]],"date-time":"2015-07-07T08:43:03Z","timestamp":1436258583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study"],"prefix":"10.1038","volume":"6","author":[{"given":"Pei-Lung","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyang-Rong","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Chung","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hsin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Chung","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Shang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keh Sung","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen-Yu","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ying","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Yih","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ching","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Tsong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy Shen-Jang","family":"Fann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Shiung","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Chun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,7]]},"reference":[{"key":"BFncomms8633_CR1","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1056\/NEJM200010263431707","volume":"343","author":"AP Weetman","year":"2000","unstructured":"Weetman, A. 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