DNA Methylation–Mediated Downregulation of SDK1 Promotes COPD Progression: A Multi-Omics Mendelian Randomization Study

Oct 23, 2025International journal of chronic obstructive pulmonary disease

Lower SDK1 Levels Caused by DNA Methylation May Promote COPD Progression

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Abstract

Eight putative causal genes for COPD were identified, with increased gene expression significantly associated with a reduced risk of COPD (β = -0.124, P = 0.002).

  • Methylation at the intronic CpG site cg07526904 is associated with lower gene expression (β = -0.148, P = 0.002) and elevated COPD susceptibility (β = 0.036, P = 0.038).
  • Expression is suggested to mediate approximately 51.9% of the total effect of cg07526904 on COPD risk (β = 0.018, P = 0.038).
  • The findings indicate a potential epigenetic pathway influencing COPD risk through gene expression regulation.

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Key numbers

0.036
Increase in COPD Risk
Effect size for the association between cg07526904 methylation and COPD risk
51.9%
Mediation Proportion
Proportion of total effect mediated by SDK1 expression
-0.148
Gene Expression Decrease
Effect size for the association between cg07526904 methylation and SDK1 expression

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