Tingting Jiang1, Yuzhuo Wang2, Meng Zhu2, Yifeng Wang1, Mingtao Huang2, Guangfu Jin1, Xuejiang Guo3, Jiahao Sha3, Juncheng Dai2, Zhibin Hu4. 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.
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.
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.