title: Genetic heterogeneity of susceptibility gene in different ethnic populations: refining association study of PTPN22 for Graves' disease in a Chinese Han population.
abstract: In our previous studies, we presumed subtypes of Graves' disease (GD) may be caused by different major susceptibility genes or different variants of a single susceptibility gene. However, more evidence is needed to support this hypothesis. Single-nucleotide polymorphism (SNP) rs2476601 in PTPN22 is the susceptibility loci of GD in the European population. However, this polymorphism has not been found in Asian populations. Here, we investigate whether PTPN22 is the susceptibility gene for GD in Chinese population and further determine the susceptibility variant of PTPN22 in GD. We conducted an imputation analysis based on the results of our genome-wide association study (GWAS) in 1,536 GD patients and 1,516 control subjects. Imputation revealed that 255 common SNPs on a linkage disequilibrium (LD) block containing PTPN22 were associated with GD (P<0.05). Nine tagSNPs that captured the 255 common variants were selected to be further genotyped in a large cohort including 4,368 GD patients and 4,350 matched controls. There was no significant difference between the nine tagSNPs (P>0.05) in either the genotype distribution or allelic frequencies between patients and controls in the replication study. Although the combined analysis exhibited a weak association signal (P(combined) = 0.003263 for rs3811021), the false positive report probability (FPRP) analysis indicated it was most likely a false positive finding. Our study did not support an association of common SNPs in PTPN22 LD block with GD in Chinese Han population. This suggests that GD in different ethnic population is probably caused by distinct susceptibility genes.
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China ; Shanghai Center for Systems Biomedicine, SJTU, Shanghai, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China ; Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital Affiliated to SJTU School of Medicine, Shanghai, China.
authors.forename: Shuangxia
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Geriatric Medicine, East Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
authors.forename: Yixuan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, the Central Hospital of Xuzhou Affiliated to Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong Province, China.
authors.forename: Guanqi
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, the First Hospital Affiliated to Bengbu Medical College, Bengbu, Anhui Province, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, the Hospital Affiliated to Jiangsu University, Zhenjiang, Jiangsu Province, China.
authors.forename: Guoyue
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Endocrinology and Gout Laboratory, Medical School Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi, Shandong Province, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Du
authors.affiliation: Department of Endocrinology, Fujian Province Hospital, Fuzhou, Fujian Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital Affiliated to SJTU School of Medicine, Shanghai, China.
authors.forename: Jialun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China ; Shanghai Institute of Endocrinology and Metabolism, Ruijin Hospital Affiliated to SJTU School of Medicine, Shanghai, China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Song
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D002681:China; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006111:Graves Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22