当前位置：
X-MOL 学术
›
BMC Med. Genomics
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Genome-wide association study in Chinese cohort identifies one novel hypospadias risk associated locus at 12q13.13.
BMC Medical Genomics ( IF 2.7 ) Pub Date : 2019-12-19 , DOI: 10.1186/s12920-019-0642-0 Zhongzhong Chen 1 , Xiaoling Lin 2, 3 , Yunping Lei 4 , Haitao Chen 2 , Richard H Finnell 4 , Yaping Wang 1 , Jianfeng Xu 2, 3 , Daru Lu 2 , Hua Xie 1 , Fang Chen 1, 5, 6
BMC Medical Genomics ( IF 2.7 ) Pub Date : 2019-12-19 , DOI: 10.1186/s12920-019-0642-0 Zhongzhong Chen 1 , Xiaoling Lin 2, 3 , Yunping Lei 4 , Haitao Chen 2 , Richard H Finnell 4 , Yaping Wang 1 , Jianfeng Xu 2, 3 , Daru Lu 2 , Hua Xie 1 , Fang Chen 1, 5, 6
Affiliation
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.
更新日期：2019-12-20
京公网安备 11010802027423号