Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin

Sinjini Sikdar; Annah B Wyss; Mi Kyeong Lee; Thanh T Hoang; Marie Richards; Laura E Beane Freeman; Christine Parks; Peter S Thorne; John L Hankinson; David M Umbach; Alison Motsinger-Reif; Stephanie J London

doi:10.1136/thoraxjnl-2020-215624

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Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin

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Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin

Sinjini Sikdar, Annah B Wyss, Mi Kyeong Lee, Thanh T Hoang, Marie Richards, Laura E Beane Freeman, Christine Parks, Peter S Thorne, John L Hankinson, David M Umbach, …

Thorax, Vol.76(12), pp.1219-1226

05/07/2021

DOI: 10.1136/thoraxjnl-2020-215624

PMCID: PMC8572320

PMID: 33963087

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Abstract

RationaleGenome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene–environment interactions, but studies are few.MethodsWe analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case–control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV1, FVC and FEV1/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value<5×10−9) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r2=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions.ResultsEach trait was highly significantly associated with its GRS (all three p values<8.9×10−8). The inverse association of the GRS with FEV1/FVC was stronger for current smokers (pinteraction=0.017) or former smokers (pinteraction=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (pinteraction=0.053). No significant interactions were observed between any GRS and house dust endotoxin.ConclusionsEvaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma.

Details

Title: Subtitle: Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin
Creators: Sinjini Sikdar - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Annah B Wyss - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Mi Kyeong Lee - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Thanh T Hoang - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Marie Richards - Westat, Durham, North Carolina, USA
Laura E Beane Freeman - Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, Maryland, USA
Christine Parks - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Peter S Thorne - Department of Occupational and Environmental Health, University of Iowa, Iowa City, Iowa, USA
John L Hankinson - Hankinson Consulting, Athens, Georgia, USA
David M Umbach - Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Alison Motsinger-Reif - Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Stephanie J London - Epidemiology Branch, National Institute of Environmental Health Sciences, Durham, North Carolina, USA
Resource Type: Journal article
Publication Details: Thorax, Vol.76(12), pp.1219-1226
DOI: 10.1136/thoraxjnl-2020-215624
PMID: 33963087
PMCID: PMC8572320
NLM abbreviation: Thorax
ISSN: 0040-6376
eISSN: 1468-3296
Grant note: DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: Z01-ES043012, Z01-ES049030, Z01-ES102385, for ABW, contract no. HHSN273201600003I; DOI: 10.13039/100000054, name: National Cancer Institute, award: Z01-CP010119; name: American Recovery and Reinvestment Act (ARRA) funds, award: N01-ES-55546; DOI: 10.13039/100000002, name: National Institutes of Health, award: NIH P30 ES005605, PHR-SUPS2-S-10-00179
Language: English
Date published: 05/07/2021
Academic Unit: Civil and Environmental Engineering; Occupational and Environmental Health
Record Identifier: 9984077373202771

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