title: A replication study for three nephrolithiasis loci at 5q35.3, 7p14.3 and 13q14.1 in the Japanese population.
abstract: A previous genome-wide association study (GWAS) reported three novel nephrolithiasis-susceptibility loci at 5q35.3, 7p14.3 and 13q14.1. Here, we investigated the association of these loci with nephrolithiasis by using an independent Japanese sample set. We performed case-control association analysis using 601 patients with nephrolithiasis and 201 control subjects. We selected seven single-nucleotide polymorphisms (SNPs): rs12654812 and rs11746443 from 5q35.3 (RGS14-SLC34A1-PFN3-F12); rs12669187 and rs1000597 from 7p14.3 (INMT-FAM188B-AQP1); and rs7981733, rs1170155, and rs4142110 from 13q14.1 (DGKH (diacylglycerol kinase)), which were previously reported to be significantly associated with nephrolithiasis. rs12654812, rs12669187 and rs7981733 were significantly associated with nephrolithiasis after Bonferroni's correction (P=3.12 × 10(-3), odds ratio (OR)=1.43; P=6.40 × 10(-3), OR=1.57; and P=5.00 × 10(-3), OR=1.41, respectively). Meta-analysis of current and previous GWAS results indicated a significant association with nephrolithiasis (P=7.65 × 10(-15), 7.86 × 10(-14) and 1.06 × 10(-9), respectively). We observed a cumulative effect with these three SNPs; individuals with three or more risk alleles had a 5.9-fold higher risk for nephrolithiasis development than those with only one risk allele. Our findings elucidated the significance of genetic variation at these three loci in nephrolithiasis in the Japanese population.
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasui
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.forename: Yuji
authors.initials: Y
authors.lastname: Urabe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Usami
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mizuno
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sato
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Koichi
authors.identifier: 0000000172922686
authors.initials: K
authors.lastname: Matsuda
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D053040:Nephrolithiasis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment