Genome-wide association study identifies susceptibility loci for IgA nephropathy

Ali G. Gharavi, Krzysztof Kiryluk, Murim Choi, Yifu Li, Ping Hou, Jingyuan Xie, Simone Sanna-Cherchi, Clara J. Men, Bruce A. Julian, Robert J. Wyatt, Jan Novak, John C. He, Haiyan Wang, Jicheng Lv, Li Zhu, Weiming Wang, Zhaohui Wang, Kasuhito Yasuno, Murat Gunel, Shrikant ManeSheila Umlauf, Irina Tikhonova, Isabel Beerman, Silvana Savoldi, Riccardo Magistroni, Gian Marco Ghiggeri, Monica Bodria, Francesca Lugani, Pietro Ravani, Claudio Ponticelli, Landino Allegri, Giuliano Boscutti, Giovanni Frasca, Alessandro Amore, Licia Peruzzi, Rosanna Coppo, Claudia Izzi, Battista Fabio Viola, Elisabetta Prati, Maurizio Salvadori, Renzo Mignani, Loreto Gesualdo, Francesca Bertinetto, Paola Mesiano, Antonio Amoroso, Francesco Scolari, Nan Chen, Hong Zhang, Richard P. Lifton

Research output: Contribution to journalArticle

Abstract

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 -10'26 and 4.84-10'9 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.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalNature Genetics
Volume43
Issue number4
DOIs
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Genetics

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    Gharavi, A. G., Kiryluk, K., Choi, M., Li, Y., Hou, P., Xie, J., Sanna-Cherchi, S., Men, C. J., Julian, B. A., Wyatt, R. J., Novak, J., He, J. C., Wang, H., Lv, J., Zhu, L., Wang, W., Wang, Z., Yasuno, K., Gunel, M., ... Lifton, R. P. (2011). Genome-wide association study identifies susceptibility loci for IgA nephropathy. Nature Genetics, 43(4), 321-329. https://doi.org/10.1038/ng.787