Main Studies Integrate retrospective studies, observational studies, and Mendelian randomization (MR) study methods to systematically analyze the strength and direction of the association between depression and asthma.

Explore whether a causal relationship exists between depression and asthma, and identify potential confounding factors and effect modifiers.

Secondary Studies Screen for key confounding variables that affect the association between depression and asthma (e.g., age, gender, lifestyle, comorbidities, etc.).

Analyze the correlation between depression and the severity of asthma. Verify the stability of instrumental variables (IVs) and the reliability of causal effects in the MR study.

Key Term Supplementary Explanations Effect modifiers: Factors that alter the strength or direction of the association between an exposure (e.g., depression) and an outcome (e.g., asthma) (e.g., certain genes or medications may modify how depression influences asthma risk).

Instrumental variables (IVs): Genetic variants used in MR studies that are associated with the exposure (e.g., depression-related SNPs) but not directly associated with the outcome (e.g., asthma) except through the exposure, helping to reduce confounding and infer causality.

Inclusion Criteria For Retrospective Study

• Age ≥ 18 years old
• Complete medical records, including demographic characteristics (age, gender, ethnicity, etc.), clinical diagnosis information (diagnosis time of depression/asthma, diagnostic basis), treatment plans (medication type, dosage), and follow-up records
• Depression diagnosis conforms to relevant clinical criteria; asthma diagnosis conforms to Guidelines for the Prevention and Treatment of Bronchial Asthma (2020 Edition)

For MR Study (GWAS Data)

• Data have undergone strict quality control
• Study participants are of European ancestry (to reduce population stratification bias)
• Clear division of case group and control group, as well as available sample size information

Exclusion Criteria For Retrospective Study

• Comorbidity with other severe mental illnesses (e.g., schizophrenia, bipolar affective disorder)
• Comorbidity with severe respiratory diseases (e.g., chronic obstructive pulmonary disease [COPD], pulmonary fibrosis, lung cancer)
• Comorbidity with severe organ failure (e.g., heart, liver, or kidney failure)
• Lack of key information in medical records (e.g., diagnosis time, core symptoms, treatment plan)

For MR Study (IVs Screening)

• Single nucleotide polymorphisms (SNPs) with an association significance P-value ≥ 5×10-⁸ with the exposure (depression/asthma)
• SNPs with high linkage disequilibrium (LD, r² ≥ 0.001, distance ≤ 10000 kb)
• SNPs located in coding regions or those that may affect gene expression regulation (at risk of horizontal pleiotropy)
• SNPs with an F-statistic < 10 (at risk of weak instrumental variable bias)

Retrospective Study: Participants aged ≥ 18 years who had complete medical records (including demographic characteristics, clinical diagnosis, treatment plan, and follow-up records) between January 2015 and December 2020. Individuals with comorbid severe mental illnesses, severe respiratory diseases, severe organ failure, or missing key information in medical records were excluded.

MR Study: Participants of European ancestry, with data sourced from the PGC (Psychiatric Genomics Consortium) major depressive disorder GWAS dataset, and the combined asthma GWAS dataset from UK Biobank and GABRIEL Consortium.