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- Title
Genome-wide association study in Chinese cohort identifies one novel hypospadias risk associated locus at 12q13.13.
- Authors
Chen, Zhongzhong; Lin, Xiaoling; Lei, Yunping; Chen, Haitao; Finnell, Richard H.; Wang, Yaping; Xu, Jianfeng; Lu, Daru; Xie, Hua; Chen, Fang
- Abstract
Background: Hypospadias risk–associated gene variants have been reported in populations of European descent using genome-wide association studies (GWASs). There is little known at present about any possible hypospadias risk associations in Han Chinese populations. Methods: To systematically investigate hypospadias risk–associated gene variants in Chinese patients, we performed the first GWAS in a Han Chinese cohort consisting of 197 moderate-severe hypospadias cases and 933 unaffected controls. Suggestive loci (p < 1 × 10− 4) were replicated in 118 cases and 383 controls, as well as in a second independent validation population of 137 cases and 190 controls. Regulatory and protein-protein interactions (PPIs) were then conducted for the functional analyses of candidate variants. Results: We identified rs11170516 with the risk allele G within the SP1/SP7 region that was independently associated with moderate-severe hypospadias [SP1/SP7, rs11170516, Pcombine = 3.5 × 10− 9, odds ratio (OR) = 1.96 (1.59–2.44)]. Results also suggested that rs11170516 is associated with the expression of SP1 as a cis-expression quantitative trait locus (cis-eQTL). Protein SP1 could affect the risk of hypospadias via PPIs. Conclusions: We performed the first GWAS of moderate-severe hypospadias in a Han Chinese cohort, and identified one novel susceptibility cis-acting regulatory locus at 12q13.13, which may regulate a variety of hypospadias-related pathways by affecting proximal SP1 gene expression and subsequent PPIs. This study complements known common hypospadias risk-associated variants and provides the possible role of cis-acting regulatory variant in causing hypospadias.
- Subjects
PROTEIN-protein interactions; HYPOSPADIAS; FUNCTIONAL analysis; COHORT analysis; HYPOMAGNESEMIA; LOCUS (Genetics)
- Publication
BMC Medical Genomics, 2019, Vol 12, Issue 1, p1
- ISSN
1755-8794
- Publication type
Article
- DOI
10.1186/s12920-019-0642-0