汉族人群中IgA肾病新易感位点的发现
Identification of new susceptibility loci for IgA nephropathy in Han Chinese
目的 识别汉族人群中IgA肾病新的易感基因位点。方法 对8,313例病例和19,680例对照进行四期GWAS研究。结果 发现了ST6GAL1（3q27.3， rs7634389，OR = 1.13，P = 7.27×10-10），ACCS （11p11.2 ，rs2074038，OR = 1.14，P = 3.93×10 -9）和ODF1-KLF10（8q22.3 rs2033562,OR=1.13, P=1.41x10-9)与IgA肾病相关联。同时验证了最近报告的ITGAX-ITGAM，（位于16p11.2，rs7190997，OR = 1.22，P = 2.26×10-19）与疾病的关联性，并且在DEFA基因座内识别了三个独立的信号（rs2033562，OR = 1.13，P = 1.41×10-9）（rs2738058，P = 1.15×10-19; rs12716641，P = 9.53×10-9; rs9314614，P = 4.25×10-9，多变量关联）。分析结果同时显示了3q27.3和11p11.2上的风险变异与血细胞中mRNA表达水平密切关联，而ST6GAL1，ACCS和DEFA中风险变异的等位基因频率与IgAN发病率的地域变化相关。结论 发现了汉族人群中IgA肾病新的易感基因位点，扩大了对IgAN遗传易感性的理解，并为IgAN的分子机制提供了新的生物学见解。
IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously-identified GWAS loci explain only a fraction of disease risk. To identify novel susceptibility loci in Han Chinese, we conduct a four-stage GWAS comprising 8,313 cases and 19,680 controls. Here, we show novel associations at ST6GAL1 on 3q27.3 (rs7634389, OR=1.13, P=7.27x10-10), ACCSon 11p11.2 (rs2074038, OR=1.14, P=3.93x10-9) and ODF1-KLF10on 8q22.3 (rs2033562,OR=1.13, P=1.41x10-9), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR=1.22, P= 2.26x10-19),and identify three independent signals within the DEFA locus(rs2738058, P=1.15x10-19; rs12716641, P=9.53x10-9; rs9314614, P=4.25x10-9, multivariate association).The risk variants on 3q27.3 and 11p11.2 show strong association with mRNA expression levels in blood cells while allele frequencies of the risk variants within ST6GAL1, ACCS and DEFA correlate with geographical variation in IgAN prevalence. Our findings expand our understanding on IgAN genetic susceptibility and provide novel biological insights into molecular mechanisms underlying IgAN.
史伟、林洪丽、孙良丹、Anand K. Andiappan、Ching-Yu Cheng、陈建、张宏、E Shyong Tai、许日聪、叶琨、刘志红、陈钦开、Ishak D. Irwan、贝锦新、Soo-Hong Chew、余学清、曾益新、Tin Aung、陈楠、张福仁、Tien-Yin Wong、唐雪晴、蒋更如、徐钢、Jia-Nee Foo、张学军、Chiea-Chuen Khor、陈孟华、廖蕴华、尹沛然、Yu-Fen Goh、王金泉、Olaf Rotzschke、李明、Kai-Yee Toh、刘建军、Seang-Mei Saw、王莉、Sheng-Ping Li、Richard P Ebstein、Hui-Qi Low
内科学基础医学遗传学
肾脏病学IgA肾病全基因组关联分析
IgA nephropathygenetic susceptibilityGWAS
史伟,林洪丽,孙良丹,Anand K. Andiappan,Ching-Yu Cheng,陈建,张宏,E Shyong Tai,许日聪,叶琨,刘志红,陈钦开,Ishak D. Irwan,贝锦新,Soo-Hong Chew,余学清,曾益新,Tin Aung,陈楠,张福仁,Tien-Yin Wong,唐雪晴,蒋更如,徐钢,Jia-Nee Foo,张学军,Chiea-Chuen Khor,陈孟华,廖蕴华,尹沛然,Yu-Fen Goh,王金泉,Olaf Rotzschke,李明,Kai-Yee Toh,刘建军,Seang-Mei Saw,王莉,Sheng-Ping Li,Richard P Ebstein,Hui-Qi Low.汉族人群中IgA肾病新易感位点的发现[EB/OL].(2017-05-04)[2025-07-21].http://www.paper.edu.cn/releasepaper/content/201705-348.点此复制
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