The infertile individual analysis based on whole-exome sequencing in chinese multi-ethnic groups

Background: Infertility is a common and rapidly growing health issue around the world. The genetic analysis based on the infertile population is crucial for intervention and treatment.

Objective: To find candidate gene locus led to azoospermia in Chinese multi-ethnic groups and provide theoretical guidance for the diagnosis of genetic diseases to progressively aggravated infertility patients and sterile offspring with ART.

Methods: The study based on whole-exome sequencing (WES) was presented for genetic characteristic analysis of multi-ethnics and identification of variants related to infertility in Xinjiang area of China.

Results: The frequency of pathogenic variants showed significant ethnic differences among four main ethnics in Xinjiang. The population structure analysis confirmed that the Hui was close to the Han population, the Kazak was close to the Uygur population, and there are three ancestry components in the four ethnics. In addition, ten candidate variants potentially regulated azoospermia were detected, and KNTC1 (rs7968222: G > T) was chosen to validate the association. Through the analysis in the valid group, the frequency of rs7968222 (G > T) has a significant difference in the azoospermia population (11.76%, 8/68) and normospermia population (4.63%, 35/756) (P < 0.001). Interestingly, the proportion of people with abnormal follicle-stimulating hormone (FSH) level in the group carrying rs7968222 (G > T) was significantly higher than non-carriers (P < 0.05). Therefore, rs7968222 may regulate spermatogenesis through affecting hormone level.

Conclusion: Our study establishes the genetics analysis of Northwest China and finds a candidate gene locus KNTC1 (rs7968222: G > T), which is one of the genetic susceptibility factors for male azoospermia.