AUTHOR=He Renke , Liu Rui , Wu Haiyan , Yu Jiaen , Jiang Zhaoying , Huang Hefeng 

TITLE=The Causal Evidence of Birth Weight and Female-Related Traits and Diseases: A Two-Sample Mendelian Randomization Analysis

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.850892

DOI=10.3389/fgene.2022.850892

ISSN=1664-8021

ABSTRACT=<p><bold>Objectives</bold><bold>:</bold> A large meta-analysis indicated a more pronounced association between lower birth weight (BW) and diseases in women but less concern about the causality between BW and female-related phenotypes and diseases.</p><p><bold>Methods:</bold> Mendelian randomization (MR) analysis was used to estimate the causal relationship between two traits or diseases using summary datasets from genome-wide association studies. Exposure instrumental variables are variants that are strongly associated with traits and are tested using four different statistical methods, including the inverse variance weighting, MR-Egger, weighted median, and weighted mode in MR analysis. Next, sensitivity analysis and horizontal pleiotropy were assessed using leave-one-out and MR-PRESSO packages.</p><p><bold>Results:</bold> The body mass index (BMI) in adulthood was determined by BW (corrected β = 0.071, <italic>p</italic> = 3.19E-03). Lower BW could decrease the adult sex hormone-binding globulin (SHBG) level (β = −0.081, <italic>p</italic> = 2.08E-06), but it resulted in increased levels of bioavailable testosterone (bio-T) (β = 0.105, <italic>p</italic> = 1.25E-05). A potential inverse effect was observed between BW and menarche (corrected β = −0.048, <italic>p</italic> = 4.75E-03), and no causal association was confirmed between BW and the risk of endometriosis, leiomyoma, and polycystic ovary syndrome.</p><p><bold>Conclusion:</bold> Our results suggest that BW may play an important role and demonstrates a significant direct influence on female BMI, SHBG and bio-T levels, and menarche.</p>