title: A genome-wide association study of nephrolithiasis in the Japanese population identifies novel susceptible Loci at 5q35.3, 7p14.3, and 13q14.1.
abstract: Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51×10⁻¹², odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16×10⁻¹⁴, OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62×10⁻⁹, OR = 1.14). Subsequent analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443 with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54×10⁻⁸), suggesting a crucial role for this variation in renal function. Our findings elucidated the significance of genetic variations for the pathogenesis of nephrolithiasis.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Urabe
authors.forename: Chizu
authors.initials: C
authors.lastname: Tanikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Okada
authors.forename: Takashi
authors.initials: T
authors.lastname: Morizono
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Tsunoda
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002882:Chromosomes, Human, Pair 13; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide