PEI-LUNG CHENSHYANG-RONG SHIHWang, Pei-WenPei-WenWangLin, Ying-ChaoYing-ChaoLinChu, Chen-ChungChen-ChungChuLin, Jung-HsinJung-HsinLinChen, Szu-ChiSzu-ChiChenCHING-CHUNG CHANGTIEN-SHANG HUANGKEH-SUNG TSAIFEN-YU TSENGCHIH-YUAN WANGJIN-YING LUWEI-YIH CHIUChang, Chien-ChingChien-ChingChangChen, Yu-HsuanYu-HsuanChenChen, Yuan-TsongYuan-TsongChenFann, Cathy Shen-JangCathy Shen-JangFannWEI-SHIUNG YANGTIEN-CHUN CHANG2023-02-072023-02-072015-07-072041-1723https://scholars.lib.ntu.edu.tw/handle/123456789/627670Graves' disease is the leading cause of hyperthyroidism affecting 1.0-1.6% 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' disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10(-32)) and HLA-DRB1*08:03 (Pcombined=1.83 × 10(-9)) 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=11.13-41.48) and 6.13 (95% confidence interval=3.28-11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10(-21), 95% confidence interval=21.66-108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.enCLOZAPINE-INDUCED AGRANULOCYTOSIS; HLA; HYPERSENSITIVITY; PHARMACOGENETICS; PREDICTION; PROGRESS; HLA-B38; SYSTEM; REGIONjournal article10.1038/ncomms8633261514962-s2.0-84936760867WOS:000358857800007https://api.elsevier.com/content/abstract/scopus_id/84936760867