Transcriptome-wide association study revealed two novel genes associated with nonobstructive azoospermia in a Chinese population

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

doi:10.1016/j.fertnstert.2017.09.023

Transcriptome-wide association study revealed two novel genes associated with nonobstructive azoospermia in a Chinese population

Fertil Steril. 2017 Dec;108(6):1056-1062.e4. doi: 10.1016/j.fertnstert.2017.09.023.

Authors

Affiliations

¹ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
² Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China.
³ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China.
⁴ State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, People's Republic of China; Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China. Electronic address: zhibin_hu@njmu.edu.cn.

PMID: 29202958
DOI: 10.1016/j.fertnstert.2017.09.023

Abstract

Objective: To investigate the associations between genetically cis-regulated gene expression levels and nonobstructive azoospermia (NOA) susceptibility.

Design: Transcriptome-wide association study (TWAS).

Setting: Medical university.

Interventions: None.

Main outcome measure(s): The cis-hg² values for each gene were estimated with GCTA software. The effect sizes of cis-single-nucleotide polymorphisms (SNPs) on gene expression were measured using GEMMA software. Gene expression levels were entered into our existing NOA GWAS cohort using GEMMA software. The TWAS P-values were calculated using logistic regression models.

Result(s): Expression levels of 1,296 cis-heritable genes were entered into our existing NOA GWAS data. The TWAS results identified two novel genes as statistically significantly associated with NOA susceptibility: PILRA and ZNF676. In addition, 6p21.32, previously reported in NOA GWAS, was further validated to be a susceptible region to NOA risk.

Conclusion(s): Analysis with TWAS provides fruitful targets for follow-up functional studies.

Keywords: GWAS; NOA; TWAS; susceptibility.

MeSH terms

Asian People / genetics
Azoospermia / diagnosis
Azoospermia / ethnology
Azoospermia / genetics*
Azoospermia / physiopathology
Case-Control Studies
China
Computational Biology
DNA-Binding Proteins / genetics*
Databases, Genetic
Fertility / genetics*
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Logistic Models
Male
Membrane Glycoproteins / genetics*
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide*
Receptors, Immunologic / genetics*
Risk Factors
Transcriptome*

Substances

DNA-Binding Proteins
Membrane Glycoproteins
PILRA protein, human
Receptors, Immunologic
ZNF676 protein, human

Supplementary concepts

Azoospermia, Nonobstructive