Genome-wide Association Study Of Hypospadias Susceptibility In A Han Chinese Population

Hypospadias is one of the multi-factor congenital malformations.The etiology of hypospadias remains unknown.Rcent studies have suggested that DGKK as a major risk gene for hypospadias.The results have been proven in the European and American population,but not in the Chinese population.Objective To establish of the biobank with the biospecimen of urogenital system in a Han Chinese population.To assess the hypospadias susceptibilityin a Han Chinese population by genome-wide association study(GWAS)in stage I and stage IIMethods We established the biobank of hypospadias patients and controls in a Han Chinese population from October 2014 to June 2016.We performed a genome-wide association study(GWAS)on 200 surgery-confirmed hypospadias cases and 1008 controls and replicated genotyping of an additional 393 cases and 390 controls.Results From October 2014 to June 2016,a total of 783 cases with hypospadias and 573 cases with phimosis or buried penis were included.200 cases with hypospadias in GWAS group,583 cases with hypospadias in SNP case group,573 cases with phimosis or buried penis in the SNP control group.Two SNPs(rs2057412 and rs6685335),the P value were 8.78 x 10-9 and 4.43 x 10^-8,respectively,statistically significant difference(P < 5 x 10^-8).22 genomic regions showed no independent association with P<5.0×10^-8.But by the Meta analysis,SNPs(rs11170516)showed statistically significant after multiple testing(P=7.51×10-9).Conclusions To our knowledge this is the first study to investigate hypospadias using GWAS in a Han Chinese population.Our findings suggest rs11170516 may be involved in the etiology of hypospadias.