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BMC Medicine Sep 2023Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's...
BACKGROUND
Few studies have investigated associations between adiposity and reproductive factors using causal methods, both of which have a number of consequences on women's health. Here we assess whether adiposity at different points in the lifecourse affects reproductive factors differently and independently, and the plausibility of the impact of reproductive factors on adiposity.
METHODS
We used genetic data from UK Biobank (273,238 women) and other consortia (EGG, GIANT, ReproGen and SSGAC) for eight 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, and two adiposity traits: childhood and adulthood body size. We applied multivariable Mendelian randomization to account for genetic correlation and to estimate the causal effects of childhood and adulthood adiposity, independently of each other, on reproductive factors. Additionally, we estimated the effects of reproductive factors, independently of other relevant reproductive factors, on adulthood adiposity.
RESULTS
We found a higher childhood body size leads to an earlier age at menarche, and an earlier age at menarche leads to a higher adulthood body size. Furthermore, we find contrasting and independent effects of childhood and adulthood body size on age at first birth (beta 0.22 SD (95% confidence interval: 0.14, 0.31) vs - 2.49 (- 2.93, - 2.06) per 1 SD increase), age at last birth (0.13 (0.06,0.21) vs - 1.86 (- 2.23, - 1.48) per 1 SD increase), age at menopause (0.17 (0.09, 0.25) vs - 0.99 (- 1.39, - 0.59) per 1 SD increase), and likelihood of having children (Odds ratio 0.97 (0.95, 1.00) vs 1.20 (1.06, 1.37) per 1 SD increase).
CONCLUSIONS
Our findings demonstrate the importance of considering a lifecourse approach when investigating the inter-relationships between adiposity measures and reproductive events, as well as the use of 'age specific' genetic instruments when evaluating lifecourse hypotheses in a Mendelian randomization framework.
Topics: Female; Humans; Adiposity; Menarche; Mendelian Randomization Analysis; Menopause; Obesity
PubMed: 37697382
DOI: 10.1186/s12916-023-03051-x -
CNS Neuroscience & Therapeutics Oct 2023The relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between the age at menarche (AAM) and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS) is still up for debate. The purpose of this study was to investigate potential causal connections between them.
METHODS
Genome-wide association analysis (GWAS) of AAM conducted by the MRC-IEU consortium was utilized for association analyses of ICH and IS by two-sample Mendelian randomization (MR) study. AAM data of the within-family GWAS consortium were used as replication phase data to verify the causal relationship between each other. Inverse variance weighting (IVW) method was the primary method used in this MR study. For additional proof, the weighted median estimation, MR-Egger regression, MR-PRESSO test, and MR-Robust Adjusted Profile Score evaluation were performed. The Cochran's Q test and the MR-PRESSO global test were used, respectively, to examine the sensitivity and pleiotropy. Random effects meta-analysis was utilized to analyze the causal data from the two consortiums to further explore the causality between AAM and ICH, IS.
RESULTS
We found that the AAM was causally linked with the risk of ICH (OR = 0.48, 95% CI: 0.28-0.80, p = 0.006). On the contrary, the causal effect from AAM to IS (OR = 0.98, 95% CI: 0.91-1.06, p = 0.64) has not been confirmed. For all subtypes of ICH, we found that nonlobar intracerebral hemorrhage (NLICH, OR = 0.41, 95% CI: 0.23-0.75, p = 0.004) but not lobar intracerebral hemorrhage (LICH, OR = 0.65, 95% CI: 0.34-1.24, p = 0.19) was associated with AAM without surprise. Similarly, we used the within-family GWAS consortium data to explore causality and found that AAM may reduce the risk of ICH (OR = 0.78, 95% CI: 0.72-0.86, p = 9.5 × 10 ) and NLICH (OR = 0.68, 95% CI: 0.61-0.75, p = 3.4 × 10 ) by IVW methods, but is not related to IS (OR = 0.97, 95% CI: 0.93-1.02, p = 0.26). These findings are further supported by the meta-analysis. Both Cochran's Q test and the MR-PRESSO global test failed to detect the presence of sensitivity.
CONCLUSION
AAM and ICH, particularly NLICH, are causally related, but not LICH, IS, or its subtypes in European population.
Topics: Female; Humans; Ischemic Stroke; Genome-Wide Association Study; Menarche; Mendelian Randomization Analysis; Cerebral Hemorrhage
PubMed: 37170723
DOI: 10.1111/cns.14245