Handgrip strength and the risk of major depressive disorder: a two-sample Mendelian randomisation study

Major depressive disorder (MDD) is a common psychiatric disease and a leading cause of disability worldwide. Handgrip strength (HGS) as an objective physical fitness test is a practical index for identifying many diseases. Previous studies drew different conclusions about the relationship between HGS and MDD.

We aim to explore whether HGS has an effect on the risk of MDD.

HGS-related single-nucleotide polymorphisms identified by a genome-wide association study were used as instrumental variables in this Mendelian randomisation (MR) study. Summary data on MDD were obtained from the Psychiatric Genomics Consortium. Four methods were applied, including inverse variance weighted (IVW), MR Egger, weighted median and weighted mode. Additional sensitivity analyses, including leave-one-out, heterogeneity test, pleiotropy test and confounders identification, were conducted to test the robustness of our results.

Each 1 kg increase in left HGS is associated with a 21.95% reduction in the risk of MDD (OR_IVW = 0.781, 95% CI: 0.650 to 0.937, p=0.009), while no significant correlation exists in the estimation of right HGS (p=0.146). Sensitivity analyses demonstrated statistical significance (β_IVW = -0.195, p=0.023) after excluding some genetic loci that cause pleiotropy.

Increased left HGS is associated with a reduced risk of MDD. In the future, it may be used as an index for the clinical screening, observation and treatment of MDD.