Effectiveness of the health literacy education program for medical student clerkships: a one-group pretest-posttest study.

Major depressive disorder (MDD) is a complex psychiatric disorder characterized by persistent low mood, loss of interest or pleasure, and cognitive and physical symptoms. With an estimated 279.6 million cases in 2019 [], MDD remains a leading cause of disability and disease burden within decades [–]. Investigations into depression pathology have revealed the involvement of abnormal inflammation and immune dysfunction [, ], which also leads to a high proportion of autoimmune comorbidities []. Indeed, increasing clinical evidence has suggested an interrelationship between MDD and autoimmune thyroid disease (AITD), the most common autoimmune disease []. A large cohort-based meta-analysis suggests that patients with AITD exhibit significantly higher chances of developing depressive symptoms and receiving a diagnosis of depression []. Correspondingly, a 13-year longitudinal cohort study demonstrated that greater severity of depressive symptoms (assessed by the Patient Health Questionnaire [PHQ]) was associated with a higher risk of AITD, including hypothyroidism and hyperthyroidism []. The observed epidemiological correlation suggests the potential existence of shared underlying determinants or common biological mechanisms between these two conditions. Among these, shared genetic architecture represents a primary area of investigation. Evidence from genome-wide association studies (GWASs) has quantified this link, with research reporting a positive genetic correlation between MDD and AITD []. Polygenic risk score (PRS) analysis, which measures an individual’s genetic predisposition to a trait based on multiple single nucleotide polymorphisms (SNPs), indicates that higher levels of thyroid antibodies increase the risk of developing major depression [], and mendelian randomization (MR) methods have identified causal relationships of MDD on AITD subtypes mediated by alcohol intake []. However, these findings mainly offer a broad view of genetic overlap, and the specific pleiotropic architecture and shared biological mechanisms underlying MDD-AITD comorbidity remain to be elucidated. Here, utilizing GWAS summary statistics and individual-level whole exome sequencing (WES) genotypes from the extensive and well-characterized UK Biobank dataset, this large-scale, comprehensive study aims to provide novel insights into the genetic relationship between MDD and AITD. Briefly, we aimed to investigate the genetic correlation, causation, pleiotropic loci and shared genes, as well as shared functional modules between MDD and AITD based on findings from common and rare variant analyses.