Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6312778 | Environment International | 2016 | 9 Pages |
Abstract
Exposure to ambient air pollution (AP) exposure has been linked to type 2 diabetes (T2D) risk. Evidence on the impact of T2D genetic variants on AP susceptibility is lacking. Compared to single variants, joint genetic variants contribute substantially to disease risk. We investigated the modification of AP and diabetes association by a genetic risk score (GRS) covering 63 T2D genes in 1524 first follow-up participants of the Swiss cohort study on air pollution and lung and heart diseases in adults. Genome-wide data and covariates were available from a nested asthma case-control study design. AP was estimated as 10-year mean residential particulate matter < 10 μm (PM10). We computed count-GRS and weighted-GRS, and applied PM10 interaction terms in mixed logistic regressions, on odds of diabetes. Analyses were stratified by pathways of diabetes pathology and by asthma status. Diabetes prevalence was 4.6% and mean exposure to PM10 was 22 μg/m3. Odds of diabetes increased by 8% (95% confidence interval: 2, 14%) per T2D risk allele and by 35% (â 8, 97%) per 10 μg/m3 exposure to PM10. We observed a positive interaction between PM10 and count-GRS on diabetes [ORinteraction = 1.10 (1.01, 1.20)], associations being strongest among participants at the highest quartile of count-GRS [OR: 1.97 (1.00, 3.87)]. Stronger interactions were observed with variants of the GRS involved in insulin resistance [(ORinteraction = 1.22 (1.00, 1.50)] than with variants related to beta-cell function. Interactions with count-GRS were stronger among asthma cases. We observed similar results with weighted-GRS. Five single variants near GRB14, UBE2E2, PTPRD, VPS26A and KCNQ1 showed nominally significant interactions with PM10 (P < 0.05). Our results suggest that genetic risk for T2D may modify susceptibility to air pollution through alterations in insulin sensitivity. These results need confirmation in diabetes cohort consortia.
Keywords
HWESAPALDIAT1DHbA1cIPWGRsT2DGEIRAFBCFMAFPM10CNGPM2.5DNAEDTAEthylenediaminetetraacetic aciddeoxyribonucleic acidHardy-Weinberg equilibriumgene-environment interactiongene-environment interactionsDiabetes mellitusType 2 diabetesType 1 diabetesparticulate matterbody mass indexBMIBeta cell functionconfidence intervalminor allele frequencyGenome-wide association studiesGWASInsulin resistanceodds ratiogenetic risk scoreglycosylated haemoglobininverse probability weightingSingle nucleotide polymorphismSNP
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Authors
Ikenna C. Eze, Medea Imboden, Ashish Kumar, Arnold von Eckardstein, Daiana Stolz, Margaret W. Gerbase, Nino Künzli, Marco Pons, Florian Kronenberg, Christian Schindler, Nicole Probst-Hensch,