• PMID: 27628680
• Gene Name: ERAP1
• Condition: Non-obstructive azoospermia
• Association: Associated
• Mutation: rs11135484, Y-hg O3e(*)
• Population size: 2703
• Population details: 2703 (1,000 NOA cases and 1,703 male controls)
• Sex: Male
• Infertility type: Male infertility
• Associated genes: GWAS

Y chromosome haplogroups based genome-wide association study pinpoints revelation for interactions on non-obstructive azoospermia

Lu C, Wen Y, Hu W, Lu F, Qin Y, Wang Y, Li S, Yang S, Lin Y, Wang C, Jin L, Shen H, Sha J, Wang X, Hu Z, Xia Y.

The Y chromosome has high genetic variability with low rates of parallel and back mutations, which make up the most informative haplotyping system. To examine whether Y chromosome haplogroups (Y-hgs) could modify the effects of autosomal variants on non-obstructive azoospermia (NOA), based on our previous genome-wide association study (GWAS), we conducted a genetic interaction analysis in GWAS subjects. Logistic regression analysis demonstrated a protective effect of Y-hg O3e(*) on NOA. Then, we explored the potential interaction between Y-hg O3e(*) and autosomal variants. Our results demonstrated that there was a suggestively significant interaction between Y-hg O3e(*) and rs11135484 on NOA (Pinter = 9.89 × 10(-5)). Bioinformatic analysis revealed that genes annotated by significant single nucleotide polymorphisms (SNPs) were mainly enriched in immunological pathways. This is the first study of interactions between Y-hgs and autosomal variants on a genome-wide scale, which addresses the missing heritability in spermatogenic impairment and sheds new light on the pathogenesis of male infertility. FAU - Lu, Chuncheng AU - Lu C AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Wen, Yang AU - Wen Y AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Hu, Weiyue AU - Hu W AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Lu, Feng AU - Lu F AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Qin, Yufeng AU - Qin Y AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Ying AU - Wang Y AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Li, Shilin AU - Li S AD - State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China. FAU - Yang, Shuping AU - Yang S AD - State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China. FAU - Lin, Yuan AU - Lin Y AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Wang, Cheng AU - Wang C AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Jin, Li AU - Jin L AD - State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China. AD - Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China. FAU - Shen, Hongbing AU - Shen H AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China. AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Sha, Jiahao AU - Sha J AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China. FAU - Wang, Xinru AU - Wang X AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China. AD - Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China. FAU - Hu, Zhibin AU - Hu Z AD - State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China. AD - Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.