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- Title
Common variants in DGKK are strongly associated with risk of hypospadias.
- Authors
van der Zanden, Loes F. M.; van Rooij, Iris A. L. M.; Feitz, Wout F. J.; Knight, Jo; Donders, A Rogier T.; Renkema, Kirsten Y.; Bongers, Ernie M. H. F.; Vermeulen, Sita H. H. M.; Kiemeney, Lambertus A. L. M.; Veltman, Joris A.; Arias-Vásquez, Alejandro; Xufeng Zhang; Markljung, Ellen; Liang Qiao; Baskin, Laurence S.; Nordenskjöld, Agneta; Roeleveld, Nel; Franke, Barbara; Knoers, Nine V. A. M.
- Abstract
Hypospadias is a common congenital malformation of the male external genitalia. We performed a genome-wide association study using pooled DNA from 436 individuals with hypospadias (cases) and 494 controls of European descent and selected the highest ranked SNPs for individual genotyping in the discovery sample, an additional Dutch sample of 133 cases and their parents, and a Swedish series of 266 cases and 402 controls. Individual genotyping of two SNPs (rs1934179 and rs7063116) in DGKK, encoding diacylglycerol kinase κ, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 × 10−11 and OR = 2.3, P = 2.9 × 10−9, respectively) and in the Dutch (OR = 3.9, P = 2.4 × 10−5 and OR = 3.8, P = 3.4 × 10−5) and Swedish (OR = 2.5, P = 2.6 × 10−8 and OR = 2.2, P = 2.7 × 10−6) replication samples. Expression studies showed expression of DGKK in preputial tissue of cases and controls, which was lower in carriers of the risk allele of rs1934179 (P = 0.047). We propose DGKK as a major risk gene for hypospadias.
- Subjects
HYPOSPADIAS; MALE reproductive organs; URETHRA; HUMAN abnormalities; GENETICS; DNA
- Publication
Nature Genetics, 2011, Vol 43, Issue 1, p48
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.721