Dataset Information

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

ABSTRACT: Objectives : 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. Methods: 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. Results: The body mass index (BMI) in adulthood was determined by BW (corrected β = 0.071, p = 3.19E-03). Lower BW could decrease the adult sex hormone-binding globulin (SHBG) level (β = -0.081, p = 2.08E-06), but it resulted in increased levels of bioavailable testosterone (bio-T) (β = 0.105, p = 1.25E-05). A potential inverse effect was observed between BW and menarche (corrected β = -0.048, p = 4.75E-03), and no causal association was confirmed between BW and the risk of endometriosis, leiomyoma, and polycystic ovary syndrome. Conclusion: 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.

SUBMITTER: He R

PROVIDER: S-EPMC9412024 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

He Renke R Liu Rui R Wu Haiyan H Yu Jiaen J Jiang Zhaoying Z Huang Hefeng H

Frontiers in genetics 20220812

Objectives : 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. Methods: 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 ...[more]

PMID: 36035116

Similar Datasets

Project description:Purpose: Birth weight has a profound long-term impact on individual's predisposition to various diseases at adulthood-a hypothesis commonly referred to as the fetal origins of adult diseases. However, it is not fully clear to what extent the fetal origins of adult diseases hypothesis holds and it is also not completely known what types of adult diseases are causally affected by birth weight. Materials and methods: Mendelian randomization using multiple genetic instruments associated with birth weight was performed to explore the causal relationship between birth weight and adult diseases. The causal relationship between birth weight and 21 adult diseases as well as 38 other complex traits was examined based on data collected from 37 large-scale genome-wide association studies with up to 340,000 individuals of European ancestry. Causal effects of birth weight were estimated using inverse-variance weighted methods. The identified causal relationships between birth weight and adult diseases were further validated through extensive sensitivity analyses, bias calculation, and simulations. Results: Among the 21 adult diseases, three were identified to be inversely causally affected by birth weight after the Bonferroni correction. The measurement unit of birth weight was defined as its standard deviation (i.e., 488 g), and one unit lower birth weight was causally related to an increased risk of coronary artery disease (CAD), myocardial infarction (MI), type 2 diabetes (T2D), and BMI-adjusted T2D, with the estimated odds ratios of 1.34 [95% confidence interval (CI) 1.17-1.53], 1.30 (95% CI 1.13-1.51), 1.41 (95% CI 1.15-1.73), and 1.54 (95% CI 1.25-1.89), respectively. All these identified causal associations were robust across various sensitivity analyses that guard against various confounding due to pleiotropy or maternal effects as well as reverse causation. In addition, analysis on 38 additional complex traits did not identify candidate traits that may mediate the causal association between birth weight and CAD/MI/T2D. Conclusions: The results suggest that lower birth weight is causally associated with an increased risk of CAD, MI, and T2D in later life, supporting the fetal origins of adult diseases hypothesis.

Project description:BackgroundThe interplay between gut microbiome genera and inflammatory kidney-related diseases, such as nephrotic syndrome, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease, has been observed. However, the causal relationships between specific bacterial genera and these renal diseases have not been fully elucidated.ObjectiveTo investigate the potential causal links between different genera of the gut microbiome and the susceptibility to various renal conditions utilizing two-sample Mendelian randomization (MR) analyses.Materials and methodsGenome-wide association study (GWAS) summary statistics of gut microbiota and inflammatory kidney-related diseases were obtained from published GWASs. Two-sample MR analyses were conducted using methods including inverse-variance weighted (IVW), MR Egger, and others to identify potential causal links between gut microbial genera and renal conditions. Sensitivity analyses, including Cochran's Q test and the MR-PRESSO global test, were performed to validate the robustness of the results and detect horizontal pleiotropy. In addition, a reverse MR analysis was conducted to assess reverse causation possibilities.ResultsBy synthesizing insights from both primary and sensitivity analyses, this study unveiled critical associations of 12 bacterial genera with nephrotic syndrome, 7 bacterial genera with membranous nephropathy, 3 bacterial genera with glomerulonephritis, 4 bacterial genera with acute tubulo-interstitial nephritis, 6 bacterial genera with chronic tubulo-interstitial nephritis, and 7 bacterial genera with chronic kidney disease. Various genera were pinpointed as having either positive or negative causal relationships with these renal conditions, as evidenced by specific ranges of IVW-OR values (all P< 0.05). The congruence of the sensitivity analyses bolstered the primary findings, displaying no marked heterogeneity or horizontal pleiotropy. Notably, the reverse MR analysis with nephritis as the exposure did not reveal any causal relationships, thereby strengthening the resilience and validity of the primary associations.ConclusionThis study explored the causal associations between several gut microbial genera and the risk of several inflammatory kidney-related diseases, uncovering several associations between specific gut microbial genera and nephrotic syndrome, membranous nephropathy, glomerulonephritis, tubulo-interstitial nephritis, and chronic kidney disease. These findings enhance our understanding of the complex interplay between the gut microbiome and kidney diseases, and they will be beneficial for early diagnosis and subsequent treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets