PEI-LUNG CHENFann C.S.-J.Chang C.-C.Wu I.-L.WEI-YIH CHIULin C.-Y.WEI-SHIUNG YANGTIEN-CHUN CHANG2020-06-012020-06-0120081466-4879https://www.scopus.com/inward/record.uri?eid=2-s2.0-40449132140&doi=10.1038%2fsj.gene.6364445&partnerID=40&md5=375ad5ece82f5b3bf02e8697a9439cd3https://scholars.lib.ntu.edu.tw/handle/123456789/495442Graves' disease (GD) is a common organ-specific autoimmune disorder inherited as a complex trait. Although there has not been consensus regarding the genuine susceptibility alleles, many population-based genetic studies showed association of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with GD. In contrast, evidence utilizing family-based studies came only from the Caucasian population. Here we performed a family-based association study in the Han population in Taiwan. We enrolled 374 affected individuals and 347 unaffected family members in 151 GD pedigrees. Four single-nucleotide polymorphisms (SNP) and a short tandem repeat polymorphism (STRP) at CTLA4 were genotyped. Association of GD with a novel risk SNP at the 5′ upstream region, CTLA4_-1722_T/C (rs733618), was demonstrated (P=0.0096). We also replicated the association signal of a coding SNP, CTLA4_+49_G/A (rs231775, P=0.0219). A common haplotype composed of CTLA4_-1722_T/C and CTLA4_(AT)n (an STRP marker: UniSTS:48500) showed protective effect (P=0.0004). Our results of family-based association study, taken together with those from the Caucasian population, provide evidence that CTLA4 confers susceptibility to GD across different ethnic backgrounds.[SDGs]SDG3adenine; cytosine; cytotoxic T lymphocyte antigen 4; guanine; tyrosine; allele; article; autoimmune disease; Caucasian; controlled study; ethnic difference; evidence based medicine; family study; female; gene linkage disequilibrium; genetic analysis; genetic association; genetic polymorphism; genetic susceptibility; genetic trait; genotype; Graves disease; haplotype; human; human cell; inheritance; major clinical study; male; nucleotide sequence; pedigree analysis; population genetics; priority journal; risk assessment; short tandem repeat; single nucleotide polymorphism; Taiwan; Antigens, CD; Antigens, Differentiation; Asian Continental Ancestry Group; Female; Gene Frequency; Genetic Predisposition to Disease; Graves Disease; Humans; Linkage (Genetics); Male; Pedigree; Polymorphism, Genetic; Taiwanjournal article10.1038/sj.gene.6364445180594682-s2.0-40449132140