Causal relationship between mental disorders and abdominal aortic aneurysm: insights from the genetic perspective

Abstract Objective This study investigated the genetic link between mental disorders—depression, schizophrenia (SCZ), and bipolar disorder (BIP)—and abdominal aortic aneurysm (AAA). Methods We used global/local genetic correlation analyses and identified shared genomic loci. Bidirectional univariable Mendelian Randomization (UMR) assessed causal directions, with multivariable MR (MVMR) refining the analysis. Mediation analyses examined if known AAA risk factors influenced this relationship. Results Global correlations showed positive links between depression, SCZ, and AAA, but not BIP. Local analyses identified specific genomic regions of correlation. We found 26, 141, and 10 shared loci for AAA with depression, SCZ, and BIP, respectively. UMR indicated significant associations between genetically predicted depression (OR 1.270; 95% CI 1.071-1.504; p = 0.006) and SCZ (OR 1.047; 95% CI 1.010-1.084; p = 0.011) with AAA, but not BIP. These results were confirmed by MVMR analyses. Mediation analyses showed that smoking, hypertension, hyperlipidemia, and coronary atherosclerosis mediated the impact of depression on AAA while smoking mediated SCZ’s impact. Conclusion This study provides evidence that genetically predicted depression and SCZ are linked to an increased risk of AAA, mediated by traditional AAA risk factors.