Genome-wide association study identifies susceptibility loci for IgA nephropathy

被引：510

作者：

Gharavi, Ali G. ^{[1
]}

Kiryluk, Krzysztof ^{[1
]}

Choi, Murim ^{[2
]}

Li, Yifu ^{[1
]}

Hou, Ping ^{[1
,3
]}

Xie, Jingyuan ^{[1
,4
]}

Sanna-Cherchi, Simone ^{[1
]}

Men, Clara J. ^{[2
]}

Julian, Bruce A. ^{[5
,6
]}

Wyatt, Robert J. ^{[7
,8
]}

Novak, Jan ^{[5
,6
]}

He, John C. ^{[9
]}

Wang, Haiyan ^{[3
]}

Lv, Jicheng ^{[3
]}

Zhu, Li ^{[3
]}

Wang, Weiming ^{[4
]}

Wang, Zhaohui ^{[4
]}

Yasuno, Kasuhito ^{[2
]}

Gunel, Murat ^{[2
]}

Mane, Shrikant ^{[2
,10
]}

Umlauf, Sheila ^{[2
,10
]}

Tikhonova, Irina ^{[2
,10
]}

Beerman, Isabel ^{[2
]}

Savoldi, Silvana ^{[11
]}

Magistroni, Riccardo ^{[12
]}

Ghiggeri, Gian Marco ^{[13
]}

Bodria, Monica ^{[13
]}

Lugani, Francesca ^{[1
,13
]}

Ravani, Pietro ^{[14
]}

Ponticelli, Claudio ^{[15
]}

Allegri, Landino ^{[16
]}

Boscutti, Giuliano ^{[17
]}

Frasca, Giovanni ^{[18
]}

Amore, Alessandro ^{[19
]}

Peruzzi, Licia ^{[19
]}

Coppo, Rosanna ^{[19
]}

Izzi, Claudia ^{[20
,21
]}

Viola, Battista Fabio ^{[22
]}

Prati, Elisabetta ^{[23
]}

Salvadori, Maurizio ^{[24
]}

Mignani, Renzo ^{[25
]}

Gesualdo, Loreto ^{[26
]}

Bertinetto, Francesca ^{[27
]}

Mesiano, Paola ^{[27
]}

Amoroso, Antonio ^{[27
]}

Scolari, Francesco ^{[20
,21
]}

Chen, Nan ^{[4
]}

Zhang, Hong ^{[3
]}

Lifton, Richard P. ^{[2
]}

机构：

[1] Columbia Univ, Dept Med, Coll Phys & Surg, New York, NY 10027 USA

[2] Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA

[3] Peking Univ, Renal Div, Hosp 1, Inst Nephrol,Key Lab Renal Dis,Minist Hlth China, Beijing 100871, Peoples R China

[4] Shanghai Jiao Tong Univ, Dept Nephrol, Ruijin Hosp, Sch Med, Shanghai 200030, Peoples R China

[5] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA

[6] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[7] Bonheur Childrens Hosp, Childrens Fdn, Res Ctr, Memphis, TN USA

[8] Univ Tennessee, Ctr Hlth Sci, Div Pediat Nephrol, Memphis, TN 38163 USA

[9] Mt Sinai Sch Med, Dept Med, York, NY USA

[10] Yale Univ, Sch Med, Yale Ctr Genome Anal, New Haven, CT 06510 USA

[11] Cirie Hosp, Nephrol & Dialysis Unit, Turin, Italy

[12] Univ Policlin Modena, Div Nefrol Dialisi & Trapianto, Azienda Osped, Modena, Italy

[13] Uremia Ist Giannina Gaslini, Lab Pathophysiol, Genoa, Italy

[14] Univ Calgary, Calgary, AB T2N 1N4, Canada

[15] Ist Sci Humanitas, Div Nefrol & Dialisi, Milan, Italy

[16] Univ Parma, Nephrol Sect, Dept Clin Med Nephrol & Hlth Sci, I-43100 Parma, Italy

[17] Osped Gorizia, Dept Nephrol, Gorizia, Italy

[18] Osped Riuniti, Nephrol & Dialysis Unit, Ancona, Italy

[19] Regina Margherita Univ Hosp, Turin, Italy

[20] Univ Brescia, Montichiari, Italy

[21] Montichiari Hosp, Div Nephrol 2, Montichiari, Italy

[22] Spedali Civil Brescia, Div Nephrol, I-25125 Brescia, Italy

[23] Osped Desenzano, Dialysis Ctr, Desenzano Del Garda, Italy

[24] Careggi Univ Hosp, Renal Unit, Florence, Italy

[25] Osped Infermi, Div Nephrol, Rimini, Italy

[26] Univ Foggia, Dept Biomed Sci, Foggia, Italy

[27] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy

来源：

NATURE GENETICS | 2011年 / 43卷 / 04期

关键词：

GALACTOSE-DEFICIENT IGA1; HLA-DR; RISK; VARIANTS; CFH; HAPLOTYPE; LINKAGE; GLOMERULONEPHRITIS; IMMUNOPROTEASOME; REPLICATION;

D O I：

10.1038/ng.787

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We carried out a genome-wide association study of IgA nephropathy, a major cause of kidney failure worldwide. We studied 1,194 cases and 902 controls of Chinese Han ancestry, with targeted follow up in Chinese and European cohorts comprising 1,950 cases and 1,920 controls. We identified three independent loci in the major histocompatibility complex, as well as a common deletion of CFHR1 and CFHR3 at chromosome 1q32 and a locus at chromosome 22q12 that each surpassed genome-wide significance (P values for association between 1.59 x 10(-26) and 4.84 x 10(-9) and minor allele odds ratios of 0.63-0.80). These five loci explain 4-7% of the disease variance and up to a tenfold variation in interindividual risk. Many of the alleles that protect against IgA nephropathy impart increased risk for other autoimmune or infectious diseases, and IgA nephropathy risk allele frequencies closely parallel the variation in disease prevalence among Asian, European and African populations, suggesting complex selective pressures.

引用

页码：321 / U68

页数：9

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