동물분자생체공학연구소 주관 초청강연 52
연사 : 김승수 박사 (Columbia University Medical Center)
제목 : Functionalgenetic variants in female reproductive lifespan
일시 : 2022년 10월 13일 목요일 오후 5시
장소 : 생명과학관 서관 231호
초록
Although female fecundity decreases withage, the length of the period between the ages of menarche and menopause, named reproductive lifespan, varies greatly from 20 to 50 years. The age at which a woman experiences menopause has impacts on a broad range of health outcomes such as coronary heart disease, type 2 diabetes, respiratory disease mortality, bone fracture, ovarian cancer, breast cancer, and stomach cancer. However, the biological mechanisms underlying the genetic contributions to female reproductive aging are still unknown. We hypothesized that genetic factors impacting reproductive lifespan also influence the risk for age-related diseases. Utilizing data from the UK Biobank, we were able to calculate the reproductive lifespan of a total of 74,543 women who had no history of hysterectomy, oophorectomy, and hormone-replacement therapy. The calculated reproductive lifespans ranged from 20 to 51 years with a median of 38 years. From the 50,698 women who have genotype data, we performed genome-wide association tests and identified 4,968 candidate risk variants including 54 lead SNPs (P < 5x10-8) in 42 loci. To identify potential causal variants, we applied integrative post-GWAS analysis with public epigenomic data and prioritized 29 high-probability causal variants in 16 loci. After overlaying ovary expression quantitative traits (eQTLs), we found that 6 reproductive lifespan risk variants in 17q21.31 coincided with enhancer marks potentially target BRCA1 and a lncRNA NBR2, both of which are well-known risk factors for breast cancer. This enhancer-based BRCA1/NBR2 dysregulation indicates that there is a shared genetic architecture between female reproductive aging and breast cancer.