AUTHOR=Chen Chunlan , He Ying 

TITLE=Causal associations between autoimmune diseases and sarcopenia-related traits: a bi-directional Mendelian randomization study

JOURNAL=Frontiers in Genetics

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1325058

DOI=10.3389/fgene.2024.1325058

ISSN=1664-8021

ABSTRACT=<sec><title>Background:</title><p>Sarcopenia is common in patients with autoimmune diseases (ADs); however, the causal associations between ADs and sarcopenia remain unclear. Therefore, this study investigated the causal associations using bi-directional Mendelian randomization analysis.</p></sec><sec><title>Methods:</title><p>Exposure-related single-nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWASs). GWAS statistics for common ADs [Crohn’s disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PSO), and multiple sclerosis (MS)] and sarcopenia-related traits [hand grip strength (HGS), appendicular fat-free mass (FFM), and walking pace] were obtained from public datasets. Inverse-variance weighting as the main method was used to evaluate the causal effect.</p></sec><sec><title>Results:</title><p>Genetically predicted CD had causal effects on whole-body FFM (β = −0.005, <italic>p</italic> = 0.001), leg FFM (β<sub>left</sub> = −0.006, <italic>p</italic> = 1.8E-4; β<sub>right</sub> = −0.007, <italic>p</italic> = 2.0E-4), and arm FFM (β<sub>left</sub> = −0.005, <italic>p</italic> = 0.005; β<sub>right</sub> = −0.005, <italic>p</italic> = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (β<sub>left</sub> = −2.06, <italic>p</italic> = 2.8E-38; β<sub>right</sub> = −2.311, <italic>p</italic> = 2E-20), whole-body FFM (β = −0.842, <italic>p</italic> = 4.7E-10), leg FFM (β<sub>left</sub> = −0.666, <italic>p</italic> = 2.6E-6; β<sub>right</sub> = −0.073, <italic>p</italic> = 2.1E-3), arm FFM (β<sub>left</sub> = −0.63, <italic>p</italic> = 4.4E-6; β<sub>right</sub> = −0.736, <italic>p</italic> = 4.4E-8), and walking pace (β = −1.019, <italic>p</italic> = 6.2E-14). In the reverse direction, HGS (odds ratio [OR]<sub>left</sub> = 10.257, <italic>p</italic> = 3.6E-5; OR<sub>right</sub> = 16.445, <italic>p</italic> = 3.7E-7) had causal effects on CD, while HGS (OR<sub>left</sub> = 0.994, <italic>p</italic> = 0.004; OR<sub>right</sub> = 0.993, <italic>p</italic> = 1.4E-4), leg FFM (OR<sub>left</sub> = 1.003, <italic>p</italic> = 0.005; OR<sub>right</sub> = 1.005, <italic>p</italic> = 1.9E-4), and walking pace (OR = 0.985, <italic>p</italic> = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits.</p></sec><sec><title>Conclusion:</title><p>Our study demonstrated that the genetic susceptibility to CD and RA was associated with high risk of sarcopenia, and some sarcopenia-related traits had causal effects on CD or RA.</p></sec>