单核苷酸多态性
遗传关联
生物
遗传学
全基因组关联研究
插补(统计学)
人类白细胞抗原
单倍型
基因型
肾病
人口分层
人口
等位基因
病例对照研究
免疫学
医学
内科学
基因
糖尿病
内分泌学
环境卫生
机器学习
抗原
缺少数据
计算机科学
作者
John Feehally,Martin Farrall,Anne Boland,Daniel P. Gale,Ivo Gut,Simon Heath,Ashish Kumar,John F. Peden,Patrick H. Maxwell,David L. Morris,Sandosh Padmanabhan,Timothy J. Vyse,Anna Zawadzka,Andrew J. Rees,Mark Lathrop,Peter J. Ratcliffe
出处
期刊:Journal of The American Society of Nephrology
日期:2010-10-01
卷期号:21 (10): 1791-1797
被引量:238
标识
DOI:10.1681/asn.2010010076
摘要
Demographic and family studies support the existence of a genetic contribution to the pathogenesis of IgA nephropathy, but results from genetic association studies of candidate genes are inconsistent. To systematically survey common genetic variation in this disease, we performed a genome-wide analysis in a cohort of patients with IgA nephropathy selected from the UK Glomerulonephritis DNA Bank. We used two groups of controls: parents of affected individuals and previously genotyped, unaffected, ancestry-matched individuals from the 1958 British Birth Cohort and the UK Blood Service. We genotyped 914 affected or family controls for 318,127 single nucleotide polymorphisms (SNPs). Filtering for low genotype call rates and inferred non-European ancestry left 533 genotyped individuals (187 affected children) for the family-based association analysis and 244 cases and 4980 controls for the case-control analysis. A total of 286,200 SNPs with call rates >95% were available for analysis. Genome-wide analysis showed a strong signal of association on chromosome 6p in the region of the MHC (P = 1 × 10(-9)). The two most strongly associated SNPs showed consistent association in both family-based and case-control analyses. HLA imputation analysis showed that the strongest association signal arose from a combination of DQ loci with some support for an independent HLA-B signal. These results suggest that the HLA region contains the strongest common susceptibility alleles that predispose to IgA nephropathy in the European population.
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