Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study Rodríguez Martín, Inmaculada Villanueva Martin, Gonzalo Guillen Del Castillo, Alfredo Ortego Centeno, Norberto Callejas Rubio, José Luis Simeón Aznar, Carmen P. Martín Ibáñez, Javier Acosta Herrera, Marialbert Systemic sclerosis Telomere length Mendelian randomization Although previous studies have suggested a relationship between telomere shortening and systemic sclerosis (SSc), the association between these two traits remains poorly understood. The objective of this study was to assess the causal relationship between telomere length in leukocytes (LTL) and SSc using the two-sample Mendelian randomization approach, with the genome-wide association study data for both LTL and SSc. The results of inverse-variance weighted regression (OR = 0.716 [95% CI 0.528–0.970], p = 0.031) and the Mendelian randomization pleiotropy residual sum and outlier method (OR = 0.716 [95% CI 0.563–0.911], p = 0.035) indicate an association between telomere length and SSc. Specifically, longer genetically predicted LTL is associated with a reduced risk of SSc. Sensitivity tests highlight the significant roles of the variants rs10936599 and rs2736100 annotated to the TERC and TERT genes, respectively. Our findings suggest an influence of telomere length in leukocytes on the development of SSc. 2024-09-23T07:53:23Z 2024-09-23T07:53:23Z 2023-10-25 journal article Rodriguez-Martin, I.; Villanueva-Martin, G.; Guillen-Del-Castillo, A.; Ortego-Centeno, N.; Callejas, J.L.; Simeón-Aznar, C.P.; Martin, J.; Acosta-Herrera, M. Contribution of Telomere Length to Systemic Sclerosis Onset: A Mendelian Randomization Study. Int. J. Mol. Sci. 2023, 24, 15589. https://doi.org/10.3390/ijms242115589 https://hdl.handle.net/10481/94836 10.3390/ijms242115589 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI