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Identification of new susceptibility loci for IgA nephropathy in Han Chinese

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单位: [1]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou 510080, Guangdong, Peoples R China [2]Minist Hlth & Guangdong Prov, Key Lab Nephrol, Guangzhou 510080, Guangdong, Peoples R China [3]Agcy Sci Technol & Res, Genome Inst Singapore, Human Genet, Singapore 138672, Singapore [4]Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis, Nanjing 210002, Jiangsu, Peoples R China [5]Singapore Eye Res Inst, Singapore 169856, Singapore [6]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 119228, Singapore [7]Natl Univ Hlth Syst, Singapore 119228, Singapore [8]Agcy Sci Technol & Res, Singapore Immunol Network, Singapore 138648, Singapore [9]Ningxia Med Univ, Gen Hosp, Dept Nephrol, Ningxia 750004, Peoples R China [10]Anhui Med Univ, Inst Dermatol, Hefei 230032, Anhui, Peoples R China [11]Anhui Med Univ, Hosp 1, Dept Dermatol, Hefei 230032, Anhui, Peoples R China [12]Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei 230032, Anhui, Peoples R China [13]Shanghai Jiao Tong Univ, Sch Med, XinHua Hosp, Dept Nephrol, Shanghai 200092, Peoples R China [14]Dalian Med Univ, Affiliated Hosp 1, Dept Nephrol, Dalian 116011, Liaoning, Peoples R China [15]Guangxi Med Univ, Affiliated Hosp 1, Dept Nephrol, Nanning 530021, Peoples R China [16]Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117549, Singapore [17]Peoples Hosp Guangxi Autonomous Reg, Dept Nephrol, Nanning, Guangxi, Peoples R China [18]Natl Univ Singapore, Dept Psychol, Singapore 117570, Singapore [19]Nanchang Univ, Affiliated Hosp 1, Dept Nephrol, Nanchang 330006, Jiangxi, Peoples R China [20]Guangdong Gen Hosp, Dept Nephrol, Guangzhou 510080, Guangdong, Peoples R China [21]Natl Univ Singapore, Dept Econ, Singapore 117570, Singapore [22]Fuzhou Gen Hosp Nanjing Mil Command, Dept Nephrol, Fuzhou 350025, Fujian, Peoples R China [23]Shandong Acad Med Sci, Shandong Prov Inst Dermatol & Venereol, Jinan 250000, Shandong, Peoples R China [24]Sun Yat Sen Univ, Ctr Canc, Dept Hepatobiliary Oncol, State Key Lab Oncol South China, Guangzhou 510080, Guangdong, Peoples R China [25]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Nephrol, Wuhan 430030, Hunan, Peoples R China [26]Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore [27]Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 119228, Singapore [28]Sichuan Prov Peoples Hosp, Dept Nephrol, Chengdu 610072, Sichuan, Peoples R China [29]Shanghai Jiao Tong Univ, Sch Med, RuiJin Hosp, Dept Nephrol, Shanghai 200025, Peoples R China [30]Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510080, Guangdong, Peoples R China [31]Chinese Acad Med Sci, Peking Union Med Coll, Beijing 100730, Peoples R China [32]Peking Univ, Inst Nephrol, Hosp 1, Div Renal, Beijing 100034, Peoples R China [33]Anhui Med Univ, Sch Biol Sci, Hefei 230032, Anhui, Peoples R China [34]Anhui Med Univ, Hosp 1, Inst Dermatol, Hefei 230032, Anhui, Peoples R China
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IgA nephropathy (IgAN) is one of the most common primary glomerulonephritis. Previously identified genome-wide association study (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, odds ratio (OR) = 1.13, P = 7.27 x 10(-10)), ACCS on 11p11.2 (rs2074038, OR = 1.14, P = 3.93 x 10(-9)) and ODF1-KLF10 on 8q22.3 (rs2033562, OR = 1.13, P = 1.41 x 10(-9)), validate a recently reported association at ITGAX-ITGAM on 16p11.2 (rs7190997, OR = 1.22, P = 2.26 x 10(-19)), and identify three independent signals within the DEFA locus (rs2738058, P = 1.15 x 10(-19); rs12716641, P = 9.53 x 10(-9); s9314614, P = 4.25 x 10(-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.

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大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
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大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者单位: [1]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Nephrol, Guangzhou 510080, Guangdong, Peoples R China [2]Minist Hlth & Guangdong Prov, Key Lab Nephrol, Guangzhou 510080, Guangdong, Peoples R China
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