Air pollution and diabetes association: Modification by type 2 diabetes genetic risk score.
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.
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Ikenna C
IC
Eze
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Medea
M
Imboden
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Karolinska Institutet, Stockholm, Sweden.
Ashish
A
Kumar
Institute of Clinical Chemistry, University Hospital Zurich, Zurich, Switzerland.
Arnold
A
von Eckardstein
Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland.
Daiana
D
Stolz
Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Margaret W
MW
Gerbase
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Nino
N
Künzli
Department of Internal Medicine, Regional Hospital of Lugano, Lugano, Switzerland.
Marco
M
Pons
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Florian
F
Kronenberg
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Christian
C
Schindler
Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address: Nicole.Probst@unibas.ch.
Nicole
N
Probst-Hensch
D000328:Adult; D000368:Aged; D000393:Air Pollutants / Q000032:analysis*; D000397:Air Pollution / Q000032:analysis*; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000032:analysis*; D012307:Risk Factors; D013557:Switzerland / Q000453:epidemiology
D000393:Air Pollutants; D052638:Particulate Matter
Cross-sectional epidemiology; Diabetes mellitus; Gene-environment interactions; Genetic risk score; Particulate matter; Type 2 diabetes risk variants