Year: 2022
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Women's reproductive factors include their age at menarche and menopause, the age at which they start and stop having children and the number of children they have. Studies that have linked these factors with disease risk have largely investigated individual reproductive factors and have not considered the genetic correlation and total interplay that may occur between them. This study aimed to investigate the nature of the relationships between eight female reproductive factors. METHODS: We used data from the UK Biobank and genetic consortia with data available for the following reproductive factors: age at menarche, age at menopause, age at first birth, age at last birth, number of births, being parous, age first had sexual intercourse and lifetime number of sexual partners. Linkage disequilibrium score regression (LDSC) was performed to investigate the genetic correlation between reproductive factors. We then applied Mendelian randomisation (MR) methods to estimate the causal relationships between these factors. Sensitivity analyses were used to investigate directionality of the effects, test for evidence of pleiotropy and account for sample overlap. RESULTS: < 0.01). MR revealed potential causal relationships between many reproductive factors, including later age at menarche (1 SD increase) leading to a later age at first sexual intercourse (beta (B) = 0.09 SD, 95% confidence intervals (CI) = 0.06,0.11), age at first birth (B = 0.07 SD, CI = 0.04,0.10), age at last birth (B = 0.06 SD, CI = 0.04,0.09) and age at menopause (B = 0.06 SD, CI = 0.03,0.10). Later age at first birth was found to lead to a later age at menopause (B = 0.21 SD, CI = 0.13,0.29), age at last birth (B = 0.72 SD, CI = 0.67, 0.77) and a lower number of births (B = -0.38 SD, CI = -0.44, -0.32). CONCLUSION: This study presents evidence that women's reproductive factors are genetically correlated and causally related. Future studies examining the health sequelae of reproductive factors should consider a woman's entire reproductive history, including the causal interplay between reproductive factors.
Source: BMC Medicine
Institutions: University of Bristol, MRC Integrative Epidemiology Unit
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,690
Awards: G1131969086, Reproductive and cardio-metabolic health, G173885373, Prenatal influences on childhood health: what role for mums and dads?, G2264987658, G2538597952, G2593619404, G2786058305, G2809956348, G3233549029, G3344456887, G339482019, G3609641447, NutriPROGRAM: Early-life Nutritional Programming of Metabolic Health through Epigenetic Pathways, G4724459389, G5192599444, G5260012927, G5470336846, G5850737185, G6455880001, G6682065591, G6824590092, Epigenetic Epidemiology, Mendelian randomization to hypothesis-free causal inference, G7194418384, Mediation analysis in life course epidemiology: methodological innovation and application to studies of obesity and cardiometabolic health, G7990456425, Molecular, Genetic and Lifecourse Epidemiology, G8502142660, G8528384394, G9000036355
OpenAlex ID: W4220689928