TY - JOUR
T1 - Genome-wide scan of Graves' disease
T2 - Evidence for linkage on chromosome 5q31 in Chinese Han pedigrees
AU - Jin, Ying
AU - Teng, Weiping
AU - Ben, Songtao
AU - Xiong, Xiaoyan
AU - Zhang, Jing
AU - Xu, Shijie
AU - Shugart, Yin Yao
AU - Jin, Li
AU - Chen, Jialun
AU - Huang, Wei
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Graves' disease (GD), which is a common organ-specific autoimmune disorder, is multifactorial and develops in genetically susceptible individuals. Despite many studies of candidate genes, only associations with human leukocyte antigen and cytotoxic T lymphocyte antigen 4 have been generally detected, and the number of susceptibility genes remains unknown. To identify chromosomal regions contributing to GD, we conducted a genome-wide scan on 322 individuals from 54 Chinese Han multiplex GD pedigrees. Parametric linkage analysis revealed the strongest evidence for linkage at D5S436 on chromosome 5q31, with a maximum two-point LOD score of 2.8 and a maximum multipoint LOD score of 2.3. To further assess the significance of this suggestive finding, we typed four additional markers around D5S436 in this chromosome region, and a maximum two-point LOD score of 4.31 and a maximum multipoint LOD score of 4.12 were obtained for marker D5S2090 (with heterogeneity, α̂ = 0.38). Nonparametric multipoint analysis also showed significant excess allele sharing, with a P value as low as 0.001, at the same locus. Our findings provide evidence for a susceptibility locus for GD on chromosome 5q31 and support the existence of genetic heterogeneity in GD.
AB - Graves' disease (GD), which is a common organ-specific autoimmune disorder, is multifactorial and develops in genetically susceptible individuals. Despite many studies of candidate genes, only associations with human leukocyte antigen and cytotoxic T lymphocyte antigen 4 have been generally detected, and the number of susceptibility genes remains unknown. To identify chromosomal regions contributing to GD, we conducted a genome-wide scan on 322 individuals from 54 Chinese Han multiplex GD pedigrees. Parametric linkage analysis revealed the strongest evidence for linkage at D5S436 on chromosome 5q31, with a maximum two-point LOD score of 2.8 and a maximum multipoint LOD score of 2.3. To further assess the significance of this suggestive finding, we typed four additional markers around D5S436 in this chromosome region, and a maximum two-point LOD score of 4.31 and a maximum multipoint LOD score of 4.12 were obtained for marker D5S2090 (with heterogeneity, α̂ = 0.38). Nonparametric multipoint analysis also showed significant excess allele sharing, with a P value as low as 0.001, at the same locus. Our findings provide evidence for a susceptibility locus for GD on chromosome 5q31 and support the existence of genetic heterogeneity in GD.
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U2 - 10.1210/jc.2001-011980
DO - 10.1210/jc.2001-011980
M3 - Article
C2 - 12679476
AN - SCOPUS:0038359681
SN - 0021-972X
VL - 88
SP - 1798
EP - 1803
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -