Sarcopenia and variation in the Human Leukocyte Antigen complex.

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record. ; BACKGROUND: Aging is characterized by chronic inflammation plus muscle mass and strength loss, termed sarcopenia. Human Leukocyte Antigen (HLA) types are drivers of autoimmune disease, although with limited penetrance. We tested whether autoimmune diagnoses are associated with sarcopenia, and whether HLA types and related genetic variants associate with sarcopenia in autoimmune disease free older people. METHODS: Data from 181,301 UK Biobank European descent volunteers aged 60 - 70 with measured hand-grip strength and impedance. Logistic regression analysis estimated HLA types sarcopenia associations, adjusted for confounders and multiple testing. RESULTS: Having any autoimmune diagnosis was associated with sarcopenia (Odds Ratio 1.83, 95% Confidence Intervals 1.74-1.92, p=4.0*10-125). After excluding autoimmune diagnoses, six of 100 HLA types (allele frequency >1%) were associated with sarcopenia (low grip strength and muscle mass). Having two HLA-DQA1*03:01 alleles increased odds of sarcopenia by 19.3% (OR 1.19, CI 1.09-1.29, p=2.84*10-5), compared to no alleles. Having ≥6 of the 12 HLA alleles increased sarcopenia odds by 23% (OR 1.23 CI 1.12-1.35, p=7.28*10-6).Of 658 HLA region non-coding genetic variants previously implicated in disease, 4 were associated with sarcopenia, including rs41268896 and rs29268645 (ORs 1.08, CI 1.05-1.11, p=1.06*10-8 and 1.07, CI 1.04-1.09 p=1.5*10-6, respectively). Some HLAs associations with sarcopenia were greater in female participants. CONCLUSION: Autoimmune diagnoses are strongly associated with sarcopenia in 60 to 70 year olds. Variation in specific HLA types and non-coding SNPs are also associated with sarcopenia in older carriers free of diagnosed autoimmune diseases. Patients with sarcopenia might benefit from targeted treatment of autoimmune processes. ; Medical Research Council (MRC) ; IPA Assignment Agreement (National Institute of Aging)