Causal links between major depressive disorder and insomnia: A Mendelian randomisation study

•Our results support that a significant genetic correlation exists between MDD and insomnia.•Genetic liability to MDD confers a causal effect on insomnia, vice versa.•TCF4 is identified as a common gene for the mutual effects between MDD and insomnia. Both Major depressive disorder (MDD) and insomnia are two common mental disorders. However, the inherent and comprehensive genetic factors causing the links between MDD and insomnia are unclear yet. Here, based on GWAS results for each disorder, we used linkage disequilibrium (LD) score regression analysis and a multi-single nucleotide polymorphism (SNP) Mendelian randomization (MR) analysis to test the genetic relationships between these two diseases. Genetic correlation analyses indicated that MDD has a significant genetic correlation with insomnia (correlation ratio = 0.40 ± 0.03, P = 1.12 × 10−52). Mendelian randomization analysis indicated that liability to MDD confers a causal effect on insomnia (bxy = 0.16 ± 0.02, P = 1.11 × 10−18), while liability to insomnia confers a causal effect on MDD (bxy = 0.57 ± 0.07, P = 1.17 × 10−14). We found that the transcription factor 4 (TCF4) gene may contribute to the mutual influences between MDD and insomnia. These results provide insights into the relationships between MDD and insomnia and may have implications for policy, planning, and provision of services.