Dataset Information

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

ABSTRACT: It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD.

Purpose

A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations.

Methods

Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity.

Results

In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86-0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06-1.46, p = 6.49 × 10^-3). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study.

Conclusions

T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.

SUBMITTER: Huang G

PROVIDER: S-EPMC10511588 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

Huang Guiwu G Chen Xiong X Chen Yanbo Y Liu Wenzhou W Chen Chen C Song Weidong W Zeng Gang G

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20230612 10

It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD.<h4>Purpose</h4>A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in ...[more]

PMID: 37306802

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Project description:BackgroundOsteoporosis, which is a bone disease, is characterized by low bone mineral density and an increased risk of fractures. The heel bone mineral density is often used as a representative measure of overall bone mineral density. Lipid metabolism, which includes processes such as fatty acid metabolism, glycerol metabolism, inositol metabolism, bile acid metabolism, carnitine metabolism, ketone body metabolism, sterol and steroid metabolism, etc., may have an impact on changes in bone mineral density. While some studies have reported correlations between lipid metabolism and heel bone mineral density, the overall causal relationship between metabolites and heel bone mineral density remains unclear.Objectiveto investigate the causal relationship between lipid metabolites and heel bone mineral density using two-sample Mendelian randomization analysis.MethodsSummary-level data from large-scale genome-wide association studies were extracted to identify genetic variants linked to lipid metabolite levels. These genetic variants were subsequently employed as instrumental variables in Mendelian randomization analysis to estimate the causal effects of each lipid metabolite on heel bone mineral density. Furthermore, metabolites that could potentially be influenced by causal relationships with bone mineral density were extracted from the KEGG and WikiPathways databases. The causal associations between these downstream metabolites and heel bone mineral density were then examined. Lastly, a sensitivity analysis was conducted to evaluate the robustness of the results and address potential sources of bias.ResultsA total of 130 lipid metabolites were analyzed, and it was found that acetylcarnitine, propionylcarnitine, hexadecanedioate, tetradecanedioate, myo-inositol, 1-arachidonoylglycerophosphorine, 1-linoleoylglycerophoethanolamine, and epiandrosterone sulfate had a causal relationship with heel bone mineral density (p < 0.05). Furthermore, our findings also indicate an absence of causal association between the downstream metabolites associated with the aforementioned metabolites identified in the KEGG and WikiPathways databases and heel bone mineral density.ConclusionThis work supports the hypothesis that lipid metabolites have an impact on bone health through demonstrating a causal relationship between specific lipid metabolites and heel bone mineral density. This study has significant implications for the development of new strategies to osteoporosis prevention and treatment.

Project description:BackgroundMany existing studies indicated that patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), tend to have the risk of low total body bone mineral density (BMD), and are more likely to have osteoporosis (OS). To determine the causal relationship between IBD and bone metabolic disorders, we herein performed a two-sample Mendelian randomization analysis (TSMR) using publicly available summary statistics.MethodsSummary statistics of total body BMD, OS and IBD were downloaded from the Open Genome-Wide Association Study (GWAS), FinnGen consortium and International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). The European and East Asian populations have consisted in this Mendelian Randomization (MR) work. A range of quality control procedures were taken to select eligible instrument SNPs closely associated with total body BMD, OS and IBD. To make the conclusions more reliable, we applied five robust analytical methods, among which the inverse variance weighting (IVW) method acted as the major method. Besides, heterogeneity, pleiotropy and sensitivity were evaluated.ResultsIn the European population, the genetic association of UC on total body BMD (OR=0.97, 95%CI=0.96,0.99, P<0.001) and overall IBD on total body BMD (OR=0.98, 95%CI=0.97,1.00, P=0.013) were significant, while the effect of CD on total body BMD was not significant enough (OR=0.99, 95%CI=0.98,1.00, P=0.085). All of UC, CD and overall IBD can be the genetic risk factor of having OS with pathological fracture (UC: OR=1.13, 95%CI=1.02,1.26, P=0.024, CD: OR=1.14, 95%CI=1.05,1.25, P=0.003, overall IBD: OR=1.13, 95%CI=1.02,1.24, P=0.015). In East Asian groups, only CD had a causal relationship with OS (OR=1.04, 95% CI=1.01,1.07, P=0.019).ConclusionOur study revealed genetically predicted associations between IBD on total body BMD and OS in European and East Asian populations. This work supplemented the results of previous retrospective studies and demonstrated the necessity of BMD monitoring in patients with IBD.

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Dataset Information

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

Purpose

Methods

Results

Conclusions

Publications

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

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