Sep 13, 2019

Shared regulatory pathways reveal novel genetic correlations between grip strength and neuromuscular disorders

BioRxiv : the Preprint Server for Biology
Sreemol GokuladhasJustin O'Sullivan

Abstract

Background: Muscle weakness and muscle wasting can be a consequence of aging (sarcopenia) and neuromuscular disorders (NMD). Genome-wide association (GWA) studies have identified genetic variants associated with grip strength (GS, an inverse measure of muscle weakness) and NMD (multiple sclerosis (MS), myasthenia gravis (MG) and amyotrophic lateral sclerosis (ALS)). However, how these variants contribute to the muscle weakness caused by aging or NMD remains obscure. Methods: We have integrated GS and NMD associated SNPs in a multimorbid analysis that leverages high-throughput chromatin interaction (Hi-C) data and expression quantitative trait loci (eQTL) data to identify allele-specific gene regulation (i.e. eGenes). Pathways and shared drug targets that are enriched by colocalised eGenes were then identified using pathway and drug enrichment analysis. Results: We identified gene regulatory mechanisms (eQTL-eGene effects) associated with GS, MG, MS, and ALS. The eQTLs associated with GS regulate a subset of eGenes that are also regulated by the eQTLs of MS, MG, and ALS. Yet, we did not find any eGenes commonly regulated by all four phenotypes associated eQTLs. By contrast, we identified three pathways (mTOR signaling, axon guid...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Biochemical Pathway
Quantitative Trait Loci
Advice
Alcoholic Intoxication, Chronic
Mtor Signaling Pathway BioCarta
Substance Abuse Detection
Amyotrophic Lateral Sclerosis
Mass Spectrometry
Pharmacologic Substance

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