Abstract
Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by elevated pulmonary artery pressure, leading to right heart failure, and mortality. The role of telomere length, a marker of biological aging, in PAH remains unclear. We utilized summary-level data from genome-wide association studies for various measures of telomere length and PAH. Single nucleotide polymorphisms associated with telomere length at a genome-wide significance level were used as instrumental variables. The inverse variance weighted method was the primary analysis, with sensitivity analyses including the weighted median and Mendelian randomization-Egger regression. The odds ratios and 95% confidence intervals (CI) were calculated to estimate the causal effect of telomere length on PAH risk. The Mendelian randomization analyses revealed no significant causal association between overall telomere length and PAH (odds ratios per standard deviation increase = 1.229, 95% CI: 0.469-3.222, P = .676). Similar null findings were observed for granulocyte, lymphocyte, naive T-cell, memory T-cell, B-cell, and natural killer-cell telomere lengths. Sensitivity analyses confirmed the robustness of the results, with no evidence of horizontal pleiotropy or significant influence of individual single nucleotide polymorphisms on the overall estimates. This Mendelian randomization study didn't support a causal association between telomere length and PAH.