Common variants in DGKK are strongly associated with risk of hypospadias
until further notice
SourceNature Genetics, 43, 1, (2011), pp. 48-50
Article / Letter to editor
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Epidemiology, Biostatistics & HTA
SubjectDCN 1: Perception and Action; DCN 2: Functional Neurogenomics; IGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 3: Genomic disorders and inherited multi-system disorders DCN 2: Functional Neurogenomics; IGMD 9: Renal disorder; NCEBP 12: Human Reproducion IGMD 3: Genomic disorders and inherited multi-system disorders; NCEBP 12: Human Reproduction IGMD 9: Renal disorder; NCEBP 1: Molecular epidemiology; NCEBP 1: Molecular epidemiology ONCOL 5: Aetiology, screening and detection; NCEBP 2: Evaluation of complex medical interventions; NCMLS 6: Genetics and epigenetic pathways of disease; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of disease IGMD 9: Renal disorder
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 kappa, produced compelling evidence for association with hypospadias in the discovery sample (allele-specific odds ratio (OR) = 2.5, P = 2.5 x 10(1)(1) and OR = 2.3, P = 2.9 x 10, respectively) and in the Dutch (OR = 3.9, P = 2.4 x 10 and OR = 3.8, P = 3.4 x 10) and Swedish (OR = 2.5, P = 2.6 x 10 and OR = 2.2, P = 2.7 x 10) 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.
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