title: Y chromosome haplogroups based genome-wide association study pinpoints revelation for interactions on non-obstructive azoospermia.
abstract: 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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Chuncheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.affiliation: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Shilin
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.|Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Jiahao
authors.initials: J
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
mesh_terms: D053713:Azoospermia / Q000235:genetics*; D016022:Case-Control Studies; D041322:Chromosomes, Human, Y / Q000235:genetics*; D003198:Computer Simulation; D063990:Gene Ontology; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics