A genetic correlation and bivariate genome-wide association study of grip strength and depression

Abstract

Grip strength is an important biomarker reflecting muscle strength, and depression is a psychiatric disorder all over the world. Several studies found a significant inverse association between grip strength and depression, and there is also evidence for common physiological mechanisms between them. We used twin data from Qingdao, China to calculate genetic correlations, and we performed a bivariate GWAS to explore potential SNPs, genes, and pathways in common between grip strength and depression. 139 pairs of Dizygotic twins were used for bivariate GWAS. VEAGSE2 and PASCAL software were used for gene-based analysis and pathway enrichment analysis, respectively. And the resulting SNPs were subjected to eQTL analysis and pleiotropy analysis. The genetic correlation coefficient between grip strength and depression was -0.41 (-0.96, -0.15). In SNP-based analysis, 7 SNPs exceeded the genome-wide significance level (P<5×10−8) and a total of 336 SNPs reached the level of suggestive significance (P<1×10−5). Gene-based analysis and pathway-based analysis identified genes and pathways related to muscle strength and the nervous system. The results of eQTL analysis were mainly enriched in tissues such as the brain, thyroid, and skeletal muscle. Pleiotropy analysis shows that 9 of the 15 top SNPs were associated with both grip strength and depression. In conclusion, this bivariate GWAS identified potentially common pleiotropic SNPs, genes, and pathways in grip strength and depression.

Depression and Hand-Grip: Unraveling the Association

“…In a groundbreaking study, Zhang et al [ 22 ] explored the shared genetic variation between depression and grip strength using twin data from Qingdao, China. They discovered potential genetic correlations, Single Nucleotide Polymorphisms (SNPs), genes, and pathways common to both conditions [ 22 ].…”

“…In a groundbreaking study, Zhang et al [ 22 ] explored the shared genetic variation between depression and grip strength using twin data from Qingdao, China. They discovered potential genetic correlations, Single Nucleotide Polymorphisms (SNPs), genes, and pathways common to both conditions [ 22 ]. The study revealed a moderate genetic correlation between grip strength and depression, with a genetic correlation coefficient of -0.41 (-0.96, -0.15), indicating a shared genetic basis [ 22 ].…”

“…They discovered potential genetic correlations, Single Nucleotide Polymorphisms (SNPs), genes, and pathways common to both conditions [ 22 ]. The study revealed a moderate genetic correlation between grip strength and depression, with a genetic correlation coefficient of -0.41 (-0.96, -0.15), indicating a shared genetic basis [ 22 ]. Key findings in the SNP-based analysis included rs117744620, located in the LRR1 gene on chromosome 14, which exceeded the genome-wide significance level.…”

“…Among the top 60 SNPs with suggested levels of association, three SNPs (rs75534602, rs117533783, rs78161270) were located near the DDC gene [ 22 ]. The DDC gene has been linked to postpartum anxiety [ 28 ] and aromatic L-amino acid decarboxylase deficiency (AADCD), which include early-onset hypotonia [ 29 ] as a primary symptom.…”

“…In gene-based analysis, two significant genes, GTF2H2C_2 and GTF2H2C were identified, but their relationship with the phenotype remains unclear due to insufficient research [ 22 ]. Several genes with nominal significance levels were found to be associated with grip strength and depression, such as FNBP1, MOG, SACS, KMO, TECPR2, and MGTA5 [ 22 ].…”