# A study on the genetic comorbidity between autoimmune diseases and pulmonary hypertension: an observational study and POST-GWAS analysis

## TL;DR

This study explores the genetic links between autoimmune diseases and pulmonary hypertension, finding shared risk factors and potential causal relationships.

## Contribution

The study identifies specific autoimmune diseases genetically correlated with pulmonary hypertension and suggests possible causal directions.

## Key findings

- Type 1 diabetes mellitus and primary biliary cholangitis show significant genetic correlation with pulmonary hypertension.
- Pulmonary hypertension may trigger the development of systemic lupus erythematosus according to reverse MR analysis.
- Rheumatoid arthritis is associated with an increased risk of pulmonary hypertension in real-world data.

## Abstract

Background: The causal relationship between various prevalent autoimmune diseases (ADs) and pulmonary hypertension (PH) has yet to be fully understood, and the contribution of genetic factors to their coexistence remains largely unexplored.

Methods: We utilized Post-GWAS and the Medical Information Mart for Intensive Care (MIMIC) database to investigate the relationship between autoimmune diseases and PH.

Results: After a series of MR Analyses, only Type 1 diabetes Mellitus (T1DM) (OR = 1.06, 95% CI 0.99-1.13, P = 0.083; OR = 1.07, 95% CI 1.02-1.13, P = 0.005) and primary biliary cholangitis (PBC) (OR = 1.10, 95% CI 1.05-1.15, P = 8.22E-5; OR = 1.08, 95% CI 1.03-1.14, P = 0.002) emerged as significantly correlated with PH. Additionally, reverse MR indicated that PH could trigger the development of systemic lupus erythematosus (SLE) (OR=1.090, 95% CI = 1.014-1.171, P = 0.014). An observational study using real-world data found a clear association between rheumatoid arthritis and increased risk of PH after adjusting confounding various variables (OR = 1.39, 95% CI 1.11-1.75, P = 0.005). Furthermore, the genetic correlation results between the diseases: T1DM & PAH: P(LDSC) = 1.20e-11, P(GNOVA) = 3.36e-08; PBC & PAH: P(LDSC) = 9.40e-07, P
(GNOVA) = 5.17e-05.

Conclusions: Our study indicates a genetic correlation and shared risk genes between PH and autoimmune diseases, offering insights into the mechanisms underlying their co-occurrence and potential implications for future therapeutic strategies.