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Air pollution and diabetes association : modification by type 2 diabetes genetic risk score

Eze, Ikenna C. and Imboden, Medea and Kumar, Ashish and von Eckardstein, Arnold and Stolz, Daiana and Gerbase, Margaret W. and Künzli, Nino and Pons, Marco and Kronenberg, Florian and Schindler, Christian and Probst-Hensch, Nicole. (2016) Air pollution and diabetes association : modification by type 2 diabetes genetic risk score. Environment international, 94. pp. 263-271.

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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 <10μm (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 22μg/m(3). Odds of diabetes increased by 8% (95% confidence interval: 2, 14%) per T2D risk allele and by 35% (-8, 97%) per 10μg/m(3) 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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Epidemiology and Public Health (EPH) > Chronic Disease Epidemiology > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
03 Faculty of Medicine > Departement Public Health > Sozial- und Präventivmedizin > Genetic Epidemiology of Non-Communicable Diseases (Probst-Hensch)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Imboden, Medea and Kumar, Ashish and Kumar, Ashish and Künzli, Nino and Schindler, Christian and Eze, Ikenna C. and Probst Hensch, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0160-4120
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:20 Oct 2017 13:15
Deposited On:31 Aug 2016 12:22

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