Volume 108, Issue 6, Pages 1056–1062.e4

Authors:

Tingting Jiang, M.D., Yuzhuo Wang, M.D., Meng Zhu, M.D., Yifeng Wang, M.D., Mingtao Huang, M.D., Guangfu Jin, Ph.D., Xuejiang Guo, Ph.D., Jiahao Sha, Ph.D., Juncheng Dai, Ph.D., Zhibin Hu, Ph.D.

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.

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