Genetic Predisposition to Allergic Rhinitis May Be a Causal Risk Factor for Bipolar Disorder and Major Depressive Disorder

Abstract There is increasing evidence suggest a link between allergic rhinitis (AR) and psychiatric disorders. However, casual associations between these variables remain uncertain. We performed bi-directional two-sample Mendelian Randomization (MR) to examine the causality association of AR with 11 different psychiatric disorders or relevant traits. MR was conducted using the inverse-variance weighted method (IVW), MR-Egger and weighted median methods. Sensitivity analyses included the MR-Egger regression and MR pleiotropy residual sum and outlier test. AR from 2 different GWAS data was positively associated with bipolar disorder (OR=1.649, 95% CI: 1.077-2.526; P=0.021; OR=1.599; 95%CI 1.058-2.417; P=0.026) and major depressive disorder (OR=1.539; 95%CI 1.007-2.353; P=0.047), but not other psychiatric illnesses. Bidirectional analyses showed that bipolar disorder is negatively associated with AR (OR=0.964; 95%CI: 0.936-0.993; P=0.015). There was no evidence for potential causal schizophrenia and effects of attention deficit/hyperactivity disorder on risk of AR by MR method, but MR pleiotropy residual outlier test suggested that attention deficit/hyperactivity disorder is negatively associated with AR after outlier correction (OR=0.976, 95%CI: 0.958-0.995, P=0.012). This MR study indicated that AR was a causal risk factor for bipolar disorder and major depressive disorder, but not for other psychiatric disorders. Bipolar disorder and attention deficit/hyperactivity disorder may be a protective factor for AR. Further studies could be carried out to unravel the underlying mechanism in AR and psychiatric disorders.