Fine mapping the MHC region identified rs4997052 as a new variant associated with nonobstructive azoospermia in Han Chinese males

Huang, Mingtao; Zhu, Meng; Jiang, Tingting; Wang, Yifeng; Wang, Cheng; Jin, Guangfu; Guo, Xuejiang; Sha, Jiahao; Dai, Juncheng; Wang, Xiaoming; Hu, Zhibin

doi:10.1016/j.fertnstert.2018.08.052

Cited by 8 publications

(9 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later on, the two GWASs performed in Chinese populations, and the follow-up study of one of them, also highlighted this genomic region as the top associated signal with NOA across the whole genome 13 – 15 . Additional evidence of the major involvement of the MHC class II in NOA was also generated by two recent studies, including an independent meta-analysis and a fine-mapping of this region using GWAS data, both from Han Chinese, in which the haplotype HLA-DRB1*1302 was confirmed as a molecular marker for NOA 41 , 42 .…”

Section: Discussionmentioning

confidence: 84%

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

et al. 2022

View full text Add to dashboard Cite

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.

show abstract

Section: Discussionmentioning

confidence: 84%

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

et al. 2022

View full text Add to dashboard Cite

show abstract

“…15 Recent studies have successfully identified several susceptibility variants within the MHC region in many diseases, and fine-mapping has been proved to be a powerful analysis in these studies. [30][31][32][33][34][35][36][37][38][39][40] In the present study, we imputed the HLA variants based on the newly developed Chinese Han reference panel, 21 and identified 2 variants that independently confer risk for HBV-related HCC. SNP rs114401688 was in perfect LD with the top signal in our previous GWAS, rs9275319.…”

Section: Discussionmentioning

confidence: 99%

Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese

Mai

Chen

et al. 2021

JHC

View full text Add to dashboard Cite

Introduction Genome-wide association studies identified susceptibility loci in the major histocompatibility complex region for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, the causal variants underlying HBV-related HCC pathogenesis remain elusive. Methods With a total of 1,161 HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and evaluated the associations of these variants with the risk of HBV-related HCC. Conditional analyses were used to identify independent signals associated with the risk of HBV-related HCC (P false-discovery rate (FDR) <0.20). A total of 14,930 variants within the MHC region were genotyped or imputed. Results We identified two variants, rs114401688 (P = 1.05 × 10 −6 , P FDR = 2.43 × 10 −3 ) and rs115126566 (P = 9.04 × 10 −5 , P FDR = 1.77 × 10 −1 ), that are independently associated with the risk of HBV-related HCC. Single nucleotide polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously reported SNP rs9275319. In the current study, we found that its association with HCC could be explained by HLA-DQB1*04 and HLA-DRB1*04. SNP rs115126566 is a novel risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 through enhancer-mediated mechanisms. HLA zygosity analysis showed that homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of HCC (P = 0.10) and the risk was more pronounced in the older age group (age ≥50, P = 0.03). Discussion Our findings further the understanding of the genetic basis for HBV-related HCC predisposition in chronic HBV carriers.

show abstract

“…Within the SC interactome, several proteins are potentially involved in meiotic cell division or gametogenesis, including the spindle and kinetochore-associated protein 1(SKA1) [94], nuclear RNA export factor 1 (NXF1) [95], cell division cycle 37 (CDC37) [96], the coiled-coil alpha-helical rod protein 1 (CCHCR1) [97], intraflagellar transport protein 20 (IFT20) [98], spermatogenesis and centriole-associated 1 like (SPATC1L) [99], and hook microtubule tethering protein 1 (HOOK1) [100]. It will be important to confirm whether these interactions exist in vivo and whether abnormal interactions between them may contribute to human infertility.…”

Section: Sc Protein Interaction Networkmentioning

confidence: 99%

Alterations in synaptonemal complex coding genes and human infertility

Zhang¹,

Liu²,

Gao³

2022

Int. J. Biol. Sci.

View full text Add to dashboard Cite

About 10% of reproductive-aged couples suffer from infertility. However, the genetic causes of human infertility cases are largely unknown. Meiosis produces haploid gametes for fertilization and errors in meiosis are associated with human infertility in both males and females. Successful meiosis relies on the assembly of the synaptonemal complex (SC) between paired homologous chromosomes during the meiotic prophase. The SC is ultrastructurally and functionally conserved, promoting inter-homologous recombination and crossover formation, thus critical for accurate meiotic chromosome segregation. With whole-genome/exome sequencing and mouse models, a list of mutations in SC coding genes has been linked to human infertility. Here we summarize those findings. We also analyzed SC gene variants present in the general population and presented complex interaction networks associated with SC components. Whether a combination of genetic variations and environmental factors causes human infertility demands further investigations.

show abstract

Fine mapping the MHC region identified rs4997052 as a new variant associated with nonobstructive azoospermia in Han Chinese males

Cited by 8 publications

References 38 publications

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

Fine Mapping of the MHC Region Identifies Novel Variants Associated with HBV-Related Hepatocellular Carcinoma in Han Chinese

Alterations in synaptonemal complex coding genes and human infertility

Contact Info

Product

Resources

About