Subject:
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DCN 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 |
Organization:
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Health Evidence Urology Human Genetics Cognitive Neuroscience Psychiatry |
Former Organization:
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Epidemiology, Biostatistics & HTA
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Abstract:
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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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