Dataset Information

Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.

ABSTRACT:

Background

Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).

Objective

To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia.

Design setting and participants

A total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011.

Measurements

We conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.

Results and limitations

Totally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P ?=? 0.005, 95%CI 1.58-13.4) and 1.82 (P ?=? 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings.

Conclusions

Our study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future.

SUBMITTER: Xu M

PROVIDER: S-EPMC3841155 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.

Xu Miaofei M Qin Yufeng Y Qu Jianhua J Lu Chuncheng C Wang Ying Y Wu Wei W Song Ling L Wang Shoulin S Chen Feng F Shen Hongbing H Sha Jiahao J Hu Zhibin Z Xia Yankai Y Wang Xinru X

PloS one 20131126 11

<h4>Background</h4>Oligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).<h4>Objective</h4>To investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, espec ...[more]

PMID: 24303009

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Project description:BACKGROUND:Pulmonary hypertension (PH) is a rare disease characterized by proliferation and occlusion of small pulmonary arterioles, which has been associated with a high mortality rate. The pathogenesis of PH is complex and incompletely understood, which includes both genetic and environmental factors that alter vascular structure and function. METHODS:Thus we aimed to reveal the potential genetic etiology of PH by targeting 143 tag SNPs of 14 candidate genes. Totally 208 individuals from Chinese Han population were enrolled in the present study, including 109 non-idiopathic PH patients and 99 healthy controls. RESULTS:The data revealed that 2 SNPs were associated with PH overall susceptibility at p?<?3×10-?4 after Bonferroni correction. The top hit was rs6557421 (p?=?4.5×10-?9), located within Nox3 gene on chromosome 6. Another SNP rs3744439 located in Tbx4 gene, also showed evidence of association with PH susceptibility (p?=?1.2×10-?6). The distribution of genotype frequencies of rs6557421 and rs3744439 have dramatic differences between PH patients and controls. Individuals with rs6557421 TT genotype had a 10.72-fold/14.20-fold increased risk to develop PH when compared with GG or GG/GT carriers in codominant or recessive model, respectively (TT versus GG: 95%CI?=?4.79-24.00; TT versus GG/GT: 95%CI?=?6.65-30.33). As for rs3744439, AG genotype only occurred in healthy controls but has not been observed in PH patients. We further validated the result by using 26 different populations from five regions around the globe, including African (AFR), American (AMR), East Asian (EAS), European (EUR), and South Asian (SAS). In consistent with the present case-control study's results, significantly different genotype frequencies of the observed SNPs existed between PH patients and healthy individuals from all over the world. CONCLUSIONS:The results suggested that rs6557421 variant in Nox3 and rs3744439 variant in Tbx4 might have potential effect on individual susceptibility to pulmonary hypertension, which could lead to therapeutic or diagnosis approaches in PH.

Dataset Information

Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.

Background

Objective

Design setting and participants

Measurements

Results and limitations

Conclusions

Publications

Evaluation of five candidate genes from GWAS for association with oligozoospermia in a Han Chinese population.

Similar Datasets

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