Dataset Information

Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

ABSTRACT:

Background

Musculoskeletal disorders were commonly reported in patients with multiple sclerosis. However, the underlying etiology linking Multiple Sclerosis (MS) and musculoskeletal disorders is not well studied. With large-scale Genome-Wide Association Studies (GWAS) publicly available, we conducted genetic correlation analysis to identify shared pleiotropic genetic effects between MS and musculoskeletal traits. We also conducted Mendelian Randomization (MR) to estimate the causal relation between MS and increased risks of musculoskeletal disorders.

Methods

Linkage Disequilibrium Score Regression (LDSR) analysis was performed to estimate heritability and genetic correlation. Univariable, multivariable, and bidirectional MR analyses were conducted to estimate the causal relation. These analyses were done by utilizing the recent GWAS summary statistics of MS, fracture, frailty, falls, and several musculoskeletal risk factors, including bone mineral density, lean mass, grip strengths, and vitamin D.

Results

LDSR analysis showed a moderate genetic correlation of MS with falls (RG=0.10, p=0.01) but not with fracture and frailty. Genetic variants (rs13191659) in LINC00240 gene which is associated with iron status biomarkers was found to be associated with both MS and falls. In MR analyses after excluding outlier SNPs with potential pleiotropic effects and correcting for multiple testing, MS presented no causal association with fracture and frailty but a minimal association with falls. Falls showed causally increased risks of fracture and frailty.

Conclusion

Our study suggests a potential genetic correlation with shared pleiotropic genetic effects between MS and falls. However, we didn't find evidence to support the causal relation between MS and increased risks of falls, fracture, and frailty.

SUBMITTER: Jeong S

PROVIDER: S-EPMC10516081 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

Jeong Sohyun S Tsai Ming-Ju MJ Shen Changbing C Hsu Yi-Hsiang YH

medRxiv : the preprint server for health sciences 20230913

<h4>Background</h4>Musculoskeletal disorders were commonly reported in patients with multiple sclerosis. However, the underlying etiology linking Multiple Sclerosis (MS) and musculoskeletal disorders is not well studied. With large-scale Genome-Wide Association Studies (GWAS) publicly available, we conducted genetic correlation analysis to identify shared pleiotropic genetic effects between MS and musculoskeletal traits. We also conducted Mendelian Randomization (MR) to estimate the causal relat ...[more]

PMID: 37745316

Similar Datasets

Project description:BackgroundObservational studies have associated obesity with an increased risk of multiple sclerosis (MS). However, the role of genetic factors in their comorbidity remains largely unknown. Our study aimed to investigate the shared genetic architecture underlying obesity and MS.MethodsBy leveraging data from genome-wide association studies, we investigated the genetic correlation of body mass index (BMI) and MS by linkage disequilibrium score regression and genetic covariance analyser. The casualty was identified by bidirectional Mendelian randomisation. Linkage disequilibrium score regression in specifically expressed genes and multimarker analysis of GenoMic annotation was utilised to explore single-nucleotide polymorphism (SNP) enrichment at the tissue and cell-type levels. Shared risk SNPs were derived using cross-trait meta-analyses and Heritability Estimation from Summary Statistics. We explored the potential functional genes using summary-data-based Mendelian randomization (SMR). The expression profiles of the risk gene in tissues were further examined.FindingsWe found a significantly positive genetic correlation between BMI and MS, and the causal association of BMI with MS was supported (β = 0.22, P = 8.03E-05). Cross-trait analysis yielded 39 shared risk SNPs, and the risk gene GGNBP2 was consistently identified in SMR. We observed tissue-specific level SNP heritability enrichment for BMI mainly in brain tissues for MS in immune-related tissues, and cell-type-specific level SNP heritability enrichment in 12 different immune cell types in brain, spleen, lung, and whole blood. The expressions of GGNBP2 were significantly altered in the tissues of patients with obesity or MS compared to those of control subjects.InterpretationOur study indicates the genetic correlation and shared risk genes between obesity and MS. These findings provide insights into the potential mechanisms behind their comorbidity and the future development of therapeutics.FundingThis work was funded by the National Natural Science Foundation of China (82171698, 82170561, 81300279, and 81741067), the Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), Natural Science Foundation of Guangdong Province (2022A1515012081), the Foreign Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), the Climbing Programme of Introduced Talents and High-level Hospital Construction Project of Guangdong Provincial People's Hospital (DFJH201803, KJ012019099, KJ012021143, and KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds (FWL).

Dataset Information

Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

Background

Methods

Results

Conclusion

Publications

Pleiotropic Genetic Effects between Multiple Sclerosis and Musculoskeletal Traits.

Similar Datasets

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