Evidence map›Paper›PMID 38801451›Full record

ArticleJournal of bone and mineral metabolism2024

Falls, fracture and frailty risk in multiple sclerosis: a Mendelian Randomization study to identify shared genetics.

Sohyun Jeong, Ming-Ju Tsai, Changbing Shen, Yi-Hsiang Hsu

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Article in Journal of bone and mineral metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Sohyun JeongHinda and Arthur Marcus Institution for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA.
Ming-Ju TsaiHinda and Arthur Marcus Institution for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA.
Changbing ShenDepartment of Dermatology, Peking University Shenzhen Hospital, Shenzhen, 518036, Guangdong, China.
Yi-Hsiang HsuHinda and Arthur Marcus Institution for Aging Research, Hebrew SeniorLife, Boston, MA, 02131, USA. yihsianghsu@hsl.harvard.edu.

Funding

Identifying Osteoporosis Genes by Whole Genome Sequencing and Functional Validation in Zebra FishR01AR072199 · NIAMS · HEBREW REHABILITATION CENTER FOR AGED · PI HSU, YI-HSIANG · 2017 to 2022
$3.2M
NIAMS NIH HHS R01 AR072199NIH HHS R01AR72199
6 · The paper itself

Abstract

introductionPatients with multiple sclerosis (MS) commonly present musculoskeletal disorders characterized by lower bone mineral density (BMD) and muscle weakness. However, the underlying etiology remains unclear. Our objective is to identify shared pleiotropic genetic effects and estimate the causal relationship between MS and musculoskeletal disorders. MATERIALS AND

methodsWe conducted linkage disequilibrium score regression (LDSR), colocalization, and Mendelian randomization (MR) analyses using summary statistics from recent large-scale genome-wide association studies (GWAS), encompassing MS, falls, fractures, and frailty. Additional MR analyses explored the causal relationship with musculoskeletal risk factors, such as BMD, lean mass, grip strength, and vitamin D.

resultsWe observed a moderate genetic correlation between MS and falls (RG = 0.10, P-value = 0.01) but not between MS with fracture or frailty in the LDSR analyses. MR revealed MS had no causal association with fracture and frailty but a moderate association with falls (OR: 1.004, FDR q-value = 0.018). We further performed colocalization analyses using nine SNPs that exhibited significant associations with both MS and falls in MR. Two SNPs (rs7731626 on ANKRD55 and rs701006 on OS9 gene) showed higher posterior probability of colocalization (PP.H4 = 0.927), suggesting potential pleiotropic effects between MS and falls. The nine genes are associated with central nervous system development and inflammation signaling pathways.

conclusionWe found potential pleiotropic genetic effects between MS and falls. However, our analysis did not reveal a causal relationship between MS and increased risks of falls, fractures, or frailty. This suggests that the musculoskeletal disorders frequently reported in MS patients in clinical studies are more likely attributed to secondary factors associated with disease progression and treatment, rather than being directly caused by MS itself.

Indexed as

Accidental FallsFractures, BoneFrailtyGenome-Wide Association StudyMendelian Randomization AnalysisMultiple SclerosisPolymorphism, Single NucleotideBone DensityFemaleHumansLinkage DisequilibriumRisk FactorsFallsFractureFrailtyMendelian randomizationMultiple sclerosis

Identifiers

PMID38801451
PMCPMC11147890

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.