title: Genome-wide Loci linked to non-obstructive azoospermia susceptibility may be independent of reduced sperm production in males with normozoospermia.
abstract: Non-obstructive azoospermia (NOA) is a complex, multifactorial disease. Recent genome-wide association studies (GWAS) have identified eight NOA susceptibility loci at genome-wide significance of P < 5.0 × 10(-8) in Han Chinese from southeastern, northern, and central China. To better understand the role of the variants in conferring NOA risk, we selected four GWAS loci (HLA-DRA rs3129878, PRMT6 rs12097821, SOX5 rs10842262, and PEX10 rs2477686) that were reported before 2014 to investigate their association with NOA and their potential effects on sperm production in 1177 Han males from southwest China, including 545 patients with idiopathic NOA and 632 controls with normozoospermia. The results confirmed that the HLA-DRA rs3129878 was an NOA susceptibility locus in the present population. Along with our data, meta-analyses supported the association of the four GWAS-linked loci with NOA, whereas an additive effect of the four loci on NOA susceptibility was not found. Interestingly, the normozoospermic males with the risk genotypes of rs12097821 and rs3129878 + rs10842262 + rs12097821 were observed to have higher total sperm counts relative to non-risk genotypes, suggesting that the risk alleles of the genetic loci may not be via impairing spermatogenic ability to express susceptibility to NOA. These findings may advance our understanding of the role of the NOA susceptibility loci, although the results need to be confirmed in larger samples.
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Tu
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yuanlong
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xianding
authors.initials: X
authors.lastname: Wang
authors.affiliation: Chengdu Reproductive Medicine Institute, Chengdu Women's and Children's Central Hospital, Chengdu, Sichuan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Reproductive Medicine Center, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Dachang
authors.initials: D
authors.lastname: Tao
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Medical Genetics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China yangyuan@scu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000483:Alleles; D053713:Azoospermia / Q000235:genetics*; D002681:China; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013091:Spermatogenesis / Q000235:genetics*
keywords: genome-wide association study; male infertility; non-obstructive azoospermia; single-nucleotide polymorphism; sperm; sperm production; spermatogenesis