BACKGROUNDExtensive evidence links a lower body mass index (BMI) to higher odds of depression in individuals of East Asian ancestry, differing from patterns observed in European populations. However, the shared genetic etiology underlying underweight and depression remains unclear in East Asian populations.METHODUtilizing large-scale genome-wide association study (GWAS) data, we investigated the shared genetics between BMI (N = 323,298) and depression traits (N = 286,052) through linkage disequilibrium score regression, cross-trait meta-analysis and colocalization analysis. Additionally, we evaluated causal associations using bidirectional Mendelian randomization (MR) analysis.RESULTSWe found a significantly negative genetic correlation between BMI and depression (rg = -0.19, P = 0.002). The cross-trait analysis identified 26 shared risk SNPs, including FTO and more. Moreover, the risk gene AGBL4 showed evidence of colocalization. Using the MR method, lower BMI was associated with higher odds of depression in individuals of East Asian ancestry (OR: 1.14, 95 % CI: 1.02 to 1.28, P = 0.021) but no reverse causal effect was observed.CONCLUSIONSOur study indicates a genetic correlation, shared risk genes, and causality between underweight and depression in East Asian populations. These findings provide insights into the potential mechanisms behind their comorbidity and inform the future development of therapeutics for East Asian populations.