Dataset Information

Body composition and risk of gestational diabetes mellitus: A univariable and multivariable Mendelian randomization study.

ABSTRACT:

Objective

In this study, we employed a Mendelian randomization (MR) approach to investigate the independent causal associations of six body composition traits with gestational diabetes mellitus (GDM).

Methods

Genome-wide significant levels (P < 10 × 5^-8 ) of single nucleotide polymorphisms associated with body water mass, total protein, whole body fat-free mass, weight, whole body fat mass, and body fat percentage were used as instrumental variables. Data on GDM were obtained from the FinnGen Consortium, and both univariable and multivariable Mendelian randomization were performed. We utilized five different analytical methods including inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the robustness of the results.

Results

With univariable Mendelian randomization, the risk of GDM increased per 1-standard deviation (SD) increase in weight (OR_weight = 1.297, P = 3.06 × 10^-5 ), whole body fat mass (OR_{whole body fat mass} = 1.408, P = 1.32 × 10^-6 ), and the risk of GDM increased per percent increase in body fat percentage (OR_{body fat percentage} = 1.661, P = 1.01 × 10^-8 ). Total protein had a protective effect on the risk of GDM (OR_{total protein} = 0.880, P = 0.048). However, there was no significant causal association between increases in body water mass and whole body fat-free mass per SD and the risk of GDM. Causal associations between weight, whole body fat mass, body fat percentage, and total protein with GDM were reduced to null in multivariable Mendelian randomization.

Conclusion

The present study furnishes genetic evidence to elucidate the causal relationship between body composition traits and GDM. Additionally, further studies are imperative to establish a causal connection between body composition traits and gestational diabetes mellitus.

SUBMITTER: Gao Y

PROVIDER: S-EPMC10906022 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Body composition and risk of gestational diabetes mellitus: A univariable and multivariable Mendelian randomization study.

Gao Yuan Y Zhou Min M Xu Xuan X Ma Jun Yang JY Qin Man Fen MF

Journal of diabetes investigation 20231127 3

<h4>Objective</h4>In this study, we employed a Mendelian randomization (MR) approach to investigate the independent causal associations of six body composition traits with gestational diabetes mellitus (GDM).<h4>Methods</h4>Genome-wide significant levels (P < 10 × 5<sup>-8</sup> ) of single nucleotide polymorphisms associated with body water mass, total protein, whole body fat-free mass, weight, whole body fat mass, and body fat percentage were used as instrumental variables. Data on GDM were ob ...[more]

PMID: 38013660

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Project description:BackgroundAlthough observational studies have demonstrated that blood lipids are associated with female infertility, the causality of this association remains unclear. We performed a univariable and multivariable Mendelian randomization (MR) analysis to evaluate the causal relationship between blood lipids and female infertility.MethodsSingle-nucleotide polymorphisms associated with lipid traits in univariate analysis were obtained from the Million Veteran Program (MVP) and Global Lipids Genetics Consortium (GLGC), involving up to 215,551 and 188,577 European individuals, respectively. Blood lipids in multivariate analysis were obtained from the latest genome-wide association study meta-analysis with lipid levels in 73 studies encompassing >300,000 participants. Data on female infertility were obtained from the FinnGen Consortium R6 release, which included 6481 samples and 75,450 controls. Subsequently, MR analysis was performed using inverse variance-weighted (IVW), weighted median, weighted-mode, simple-mode and MR-Egger regression to demonstrate the causal relationship between lipids and female infertility.ResultsAfter controlling confounding factors including body mass index and age at menarche, two-sample MR demonstrated that genetically predicted LDL-C and TC were causally associated with the risk of female infertility (When the genetic instruments come from the MVP database, LDL-C and female infertility, IVW OR: 1.13, 95% CI: 1.001-1.269, p = 0.047; TC and female infertility, IVW OR: 1.16, 95% CI: 1.018-1.317, p = 0.025, and when the genetic instruments came from the GLGC database, LDL-C and female infertility, IVW OR: 1.10, 95% CI: 1.008-1.210, p = 0.033; TC and female infertility, IVW OR: 1.14, 95% CI: 1.024-1.258, p = 0.015). However, the IVW estimate showed that HDL-C was not significantly associated with the risk of female infertility (when the genetic instruments came from the MVP database, IVW OR: 1.00, 95% CI: 0.887-1.128, p = 0.999; when the genetic instruments came from the GLGC database, IVW OR: 1.00, 95% CI: 0.896-1.111, p = 0.968). The multivariable MR analysis also provided evidence that LDL-C (OR: 1.12, 95% CI: 1.006-1.243, p = 0.042) was significantly associated with the risk of female infertility after considering the correlation of all lipid-related traits.ConclusionThese findings support a causal relationship between increased LDL-cholesterol and increased female infertility risk. Furthermore, the association between lipid-related traits and female infertility risk merits more studies.

Dataset Information

Body composition and risk of gestational diabetes mellitus: A univariable and multivariable Mendelian randomization study.

Objective

Methods

Results

Conclusion

Publications

Body composition and risk of gestational diabetes mellitus: A univariable and multivariable Mendelian randomization study.

Similar Datasets

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