ArticleAMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science2024
Clarifying Chronic Obstructive Pulmonary Disease Genetic Associations Observed in Biobanks via Mediation Analysis of Smoking.
Article in AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Varying case definitions of COPD have heterogenous genetic risk profiles, potentially reflective of disease subtypes or classification bias (e.g., smokers more likely to be diagnosed with COPD). To better understand differences in genetic loci associated with ICD-defined versus spirometry-defined COPD we contrasted their GWAS results with those for heavy smoking among 337,138 UK Biobank participants. Overlapping risk loci were found in/near the genes ZEB2, FAM136B, CHRNA3, and CHRNA4, with the CHRNA3 locus shared across all three traits. Mediation analysis to estimate the effects of lead genotyped variants mediated by smoking found significant indirect effects for the FAM136B, CHRNA3, and CHRNA4 loci for both COPD definitions. Adjustment for mediator-outcome confounders modestly attenuated indirect effects, though in the CHRNA4 locus for spirometry-defined COPD the proportion mediated increased an additional 8.47%. Our results suggest that differences between ICD-defined and spirometry-defined COPD associated genetic loci are not a result of smoking biasing classification.
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38827081PMC11141825What OpenQuestion holds
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