1. Genome-wide association study identifies susceptibility loci for IgA nephropathy
- Author
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Silvana Savoldi, Antonio Amoroso, Alessandro Amore, Hong Zhang, Weiming Wang, Robert J. Wyatt, Gian Marco Ghiggeri, Krzysztof Kiryluk, Francesca Lugani, Bruce A. Julian, Monica Bodria, Clara J. Men, Jingyuan Xie, Pietro Ravani, Murat Gunel, Paola Mesiano, Jicheng Lv, Renzo Mignani, Francesca Bertinetto, Prati E, Riccardo Magistroni, Isabel Beerman, Sheila Umlauf, Nan Chen, Francesco Scolari, Battista Fabio Viola, Maurizio Salvadori, Claudio Ponticelli, Haiyan Wang, Ali G. Gharavi, Yifu Li, Landino Allegri, Rosanna Coppo, John Cijiang He, Giovanni M. Frascà, Murim Choi, Jan Novak, Loreto Gesualdo, Irina Tikhonova, Kasuhito Yasuno, Zhaohui Wang, Licia Peruzzi, Li Zhu, Giuliano Boscutti, Shrikant Mane, Richard P. Lifton, Claudia Izzi, Ping Hou, and Simone Sanna-Cherchi
- Subjects
Adult ,Male ,Chromosomes, Human, Pair 22 ,030232 urology & nephrology ,Locus (genetics) ,Genome-wide association study ,Human leukocyte antigen ,Biology ,Polymorphism, Single Nucleotide ,White People ,Article ,Nephropathy ,Cohort Studies ,Major Histocompatibility Complex ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,HLA Antigens ,Risk Factors ,Complement C3b Inactivator Proteins ,Genetics ,medicine ,Humans ,GWAS ,Genetic Predisposition to Disease ,Selection, Genetic ,Allele ,Alleles ,030304 developmental biology ,IGAN ,0303 health sciences ,Neprhopathy ,Case-control study ,Glomerulonephritis, IGA ,Blood Proteins ,Odds ratio ,medicine.disease ,IgA nephropathy Genome wide scanning ,3. Good health ,Minor allele frequency ,Chromosomes, Human, Pair 1 ,Case-Control Studies ,Immunology ,Female ,Genome-Wide Association Study - 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.
- Published
- 2011
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