. Author manuscript; available in PMC: 2025 Dec 5.

Published in final edited form as: Nat Rev Genet. 2024 Mar 6;25(8):534–547. doi: 10.1038/s41576-024-00695-0

Table 2. Gene–environment effects from genome-wide interaction analyses in respiratory disease.

Environmental stimulus	COPD or lung function	Asthma
Tobacco smoke	Significant interactions with GRS for COPD and lung function in the UK Biobank data; replication needed^75,94.	Significant interaction at KLH1, with evidence of consistency across five large cohorts⁹⁶.
	Significant, replicated interactions at known COPD risk loci CHRNB4 and EGLN2⁷⁸.	Several other loci with suggestive significance^7,97–99.
	Significant but not replicated interactions at several other loci^78,95.
Outdoor air pollution	Significant but not replicated interactions between lung function and PM_2.5, PM₁₀ or NO₂ at seven loci (such as C1orf159, FAT1 and KDM3B)⁸⁰.	Suggestive evidence of an interaction effect of NO₂ on childhood asthma at B4GALT5, ADCY2 and DLG2¹⁰⁰.
	No interaction with a GRS for lung function⁸⁰.
Occupational dust and chemicals	Suggestive associations for lung function identified from cohorts that used self-reported job title as a proxy for exposure^101,102.	No genome-wide gene-environment studies.

P < 0.05 or the Bonferroni-corrected equivalent was considered evidence of replication. COPD, chronic obstructive pulmonary disease; GRS, genetic risk score PM2.5; particulate matter under 2.5 μm; PM10, particulate matter under 10 μm.