Five SNPs (rs2211122, rs4554617, rs7058226, rs7063116, and rs5915254) in DGKK were significantly associated with hypospadias (P < 0.05), with odds ratios (ORs) of 1.64-1.76.
Six SNPs (rs1934179, rs4143304, rs9969978, rs1934188, rs7063116 and rs1934190) were significantly associated with mild/moderate hypospadias (ORs >1, P < 0.05), and rs1934179 was significantly associated with severe hypospadias (OR > 1, P < 0.05).
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.