Standardizing trait selection in Mendelian randomization studies concerning sarcopenia

Abstract

Mendelian randomization (MR) is a method of using genetic variants as instrumental variables to assess the causal effect of exposures on disease outcomes. MR has gained increasing attention in the field of genetic epidemiology and has been applied to explore the causal associations in various diseases, including sarcopenia. 1 Traditional observational studies are often limited in their ability to demonstrate causal relationships. Due to cost limitations and the fact that the development of sarcopenia is a long-term process, randomized controlled trials are also difficult to conduct to confirm its causal factors. 2 MR might be a useful method to estimate the potential causal factors of sarcopenia. Searching the term 'Sarcopenia AND Mendelian Randomization' in PubMed, we found more than 70 MR studies about sarcopenia. In these studies, many potential causal associations of sarcopenia had been reported, including lifestyle, related diseases and so on. Discovering these causal factors of sarcopenia may provide potential evidence for clinical investigation. However, there was still an issue to be noted when conducting MR studies for sarcopenia: selection of the sarcopenia trait.MR was based on summary genome-wide association study (GWAS) data. Usually, when we try to obtain the summary GWAS data, most of the diseases or their specific classifications in summary GWAS were defined clearly, for example, Crohn's disease in inflammatory bowel diseases. 3 However,