Deciphering the genetic interconnection between sarcopenia and osteoporosis: SCD1

Abstract

Introduction: Sarcopenia is closely related to osteoporosis, but the causal direction of these associations remains unclear. This study aims to explore these potential causal associations from the perspective of gene regulation.

Materials and methods: Differentially expressed genes between sarcopenia and control, were identified as exposure factors, with osteoporosis serving as outcome variable, to identify key genes that had potential causal association with osteoporosis. Further analysis was conducted to investigate the causal links between key genes and sarcopenia-related characteristics. Moreover, enrichment analyses, ceRNA and Gene-Gene Interaction network were studied.

Results: Only SCD1 demonstrated a potential causal association with osteoporosis (OR = 0.9970, P = 0.0217), acting as a protective factor against the disease. The potential causal links between SCD1 and sarcopenia-related characteristics are executed. SCD1 was identified as a risk factor for low hand grip strength (OR = 1.1397, P = 0.0290), while being pinpointed as a protective factor for appendicular lean mass (OR = 0.8777, P = 0.0147), usual walking pace (OR = 0.9834, P = 0.0290), whole body fat-free mass (OR = 0.9412, P = 0.0227), and trunk fat-free mass (OR = 0.9425, P = 0.0257). All analyses passed Steiger directional test, indicating a unidirectional causal association. Moreover, indicated that SCD1 was significantly associated with metabolic pathways related to lipid biosynthesis and regulation.

Conclusion: SCD1 was identified as a protective factor for osteoporosis and a risk factor for sarcopenia. This research provides new insights for the study of sarcopenia and osteoporosis, and offers theoretical backing for the positive effects of exercise in the elderly.

Keywords: Causal inference; Genetics; Mendelian randomization; Osteoporosis; Sarcopenia.