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

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.