title: Genome-wide association study identifies susceptibility loci for IgA nephropathy.
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.
authors.affiliation: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kiryluk
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.forename: Yifu
authors.initials: Y
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Hou
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Xie
authors.forename: Simone
authors.initials: S
authors.lastname: Sanna-Cherchi
authors.forename: Clara J
authors.initials: CJ
authors.lastname: Men
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wyatt
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.forename: John C
authors.initials: JC
authors.lastname: He
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Jicheng
authors.initials: J
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.forename: Weiming
authors.initials: W
authors.lastname: Wang
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Wang
authors.forename: Kasuhito
authors.initials: K
authors.lastname: Yasuno
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
authors.forename: Shrikant
authors.initials: S
authors.lastname: Mane
authors.forename: Sheila
authors.initials: S
authors.lastname: Umlauf
authors.forename: Irina
authors.initials: I
authors.lastname: Tikhonova
authors.forename: Isabel
authors.initials: I
authors.lastname: Beerman
authors.forename: Silvana
authors.initials: S
authors.lastname: Savoldi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Magistroni
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Monica
authors.initials: M
authors.lastname: Bodria
authors.forename: Francesca
authors.initials: F
authors.lastname: Lugani
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Claudio
authors.initials: C
authors.lastname: Ponticelli
authors.forename: Landino
authors.initials: L
authors.lastname: Allegri
authors.forename: Giuliano
authors.initials: G
authors.lastname: Boscutti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Frasca
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amore
authors.forename: Licia
authors.initials: L
authors.lastname: Peruzzi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Coppo
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Battista Fabio
authors.initials: BF
authors.lastname: Viola
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Prati
authors.forename: Maurizio
authors.initials: M
authors.lastname: Salvadori
authors.forename: Renzo
authors.initials: R
authors.lastname: Mignani
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.forename: Francesca
authors.initials: F
authors.lastname: Bertinetto
authors.forename: Paola
authors.initials: P
authors.lastname: Mesiano
authors.forename: Antonio
authors.initials: A
authors.lastname: Amoroso
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D015331:Cohort Studies; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012641:Selection, Genetic; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D006680:HLA Antigens