W39. DISSECTING THE SHARED GENETIC ARCHITECTURE BETWEEN DEPRESSION AND SARCOPENIA

Depression and sarcopenia are 2 common disorders in the elderly with a high rate of comorbidity. However, the underlying shared mechanism between these 2 disorders remains unclear. The current study aimed to explore the shared genetic architecture between depression and sarcopenia, which can guide clinical practice and therapy development. Using appendicular lean mass (ALM) as the proxy of sarcopenia, we first examined the shared genetic correlation, pleiotropic enrichment and genetic causality between depression and ALM with the genome-wide association study (GWAS) datasets. Next, we applied the conjunctional false discovery rate (conjFDR) analysis to explore the shared loci between depression and ALM. Last but not least, we used expression quantitative loci (eQTL) to annotate the shared loci, aiming to explore the shared genes and pathways between depression and ALM. We found a significant negative genetic correlation and pleiotropic enrichment between depression and ALM. Moreover, with the MR method, we found that higher ALM was causally associated with a lower risk of depression, and depression was causally associated with lower ALM, indicating the bidirectional causality between depression and sarcopenia. At the SNP loci, 75 loci were found to be shared between ALM and depression, with a majority (49/75, 65.3%) of the loci having opposite effects on ALM and depression, which was consistent with the negative genetic correlation between ALM and depression. Moreover, these 49 loci were associated with the expression of 112 unique protein-coding genes in the blood, brain or skeletal muscle. These genes were enriched in pathways including "protein glycosylation" and "regulation of protein binding", which were suggested to be the shared pathogenesis mediating depression and sarcopenia. In summary, our findings revealed the shared genetic mechanism between depression and sarcopenia, which increased our understanding of these diseases' overlapping etiologies or comorbidity. Moreover, our results also provided insights into developing novel potential therapeutics based on shared genetic factors, which needed further study.