Fig. 6: Comorbidity, Mendelian randomisation and polygenic risk score analyses with depression.

a Comorbidity relationship between eight depression phenotypes⁶⁸ and each of the PUD, GORD, IBS, and IBD. Odds ratio and 95% CI were calculated based on the 2 by 2 contingency table for number of cases and controls of each of the 32 digestion-depression phenotype pairs (Supplementary Tables 19 and 20). The definitions of the eight depression phenotypes are in the Methods section. “*” represents the P value for each digestion and depression pair that remain significant after Bonferroni correction (P < 0.05/32). b Mendelian randomization (MR) results between major depression (MD) and five digestion phenotypes. The left y axis is for MD while the right y axis is for the five digestion phenotypes. The arrow for each horizontal line represents the direction from exposure trait to outcome trait relative to the y-axis labels. OR and 95% CI are represented as diamond and horizontal lines taking values from x axis. Each digestive phenotype corresponds to two horizontal lines. “R” on the right side of the horizontal line represents relaxation of significance threshold of SNP associations to obtain more SNP genetic instruments (Supplementary Table 21). The number of the SNP instruments used in analyses are shown above the diamond. The common pathological characteristics or symptoms for these phenotype-related diseases are shown on the right side (noting that pathological characteristics or symptoms are not limited to these locations). c Decile of major depression polygenic score predicts PG₊M. Odds ratio (OR) and 95% confidence intervals (CI, blue dots and orange bars) relative to decile 1 were estimated using logistic regression. The blue dashed lines shows the OR for the highest decile, OR of 1.33 for PG₊M related disorders. d OR and 95% CIs (green dots and blue bars) for top decile of PG₊M polygenic score predicting depression and psychiatric disorders in the independent GERA cohort³⁶.