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ENVIRONMENT-WIDE ASSOCIATION STUDY (EWAS) FOR TYPE 2 DIABETES IN THE MARSHFIELD PERSONALIZED MEDICINE RESEARCH PROJECT BIOBANK

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Title
ENVIRONMENT-WIDE ASSOCIATION STUDY (EWAS) FOR TYPE 2 DIABETES IN THE MARSHFIELD PERSONALIZED MEDICINE RESEARCH PROJECT BIOBANK
Published in
Biocomputing, November 2013
DOI 10.1142/9789814583220_0020
Pubmed ID
Authors

Russ B Altman, A Keith Dunker, Lawrence Hunter, Tiffany A Murray, Teri E Klein, Marylyn D Ritchie, MOLLY A. HALL, SCOTT M. DUDEK, ROBERT GOODLOE, DANA C. CRAWFORD, SARAH A. PENDERGRASS, PEGGY PEISSIG, MURRAY BRILLIANT, CATHERINE A. MCCARTY, MARYLYN D. RITCHIE

Abstract

Environment-wide association studies (EWAS) provide a way to uncover the environmental mechanisms involved in complex traits in a high-throughput manner. Genome-wide association studies have led to the discovery of genetic variants associated with many common diseases but do not take into account the environmental component of complex phenotypes. This EWAS assesses the comprehensive association between environmental variables and the outcome of type 2 diabetes (T2D) in the Marshfield Personalized Medicine Research Project Biobank (Marshfield PMRP). We sought replication in two National Health and Nutrition Examination Surveys (NHANES). The Marshfield PMRP currently uses four tools for measuring environmental exposures and outcome traits: 1) the PhenX Toolkit includes standardized exposure and phenotypic measures across several domains, 2) the Diet History Questionnaire (DHQ) is a food frequency questionnaire, 3) the Measurement of a Person's Habitual Physical Activity scores the level of an individual's physical activity, and 4) electronic health records (EHR) employs validated algorithms to establish T2D case-control status. Using PLATO software, 314 environmental variables were tested for association with T2D using logistic regression, adjusting for sex, age, and BMI in over 2,200 European Americans. When available, similar variables were tested with the same methods and adjustment in samples from NHANES III and NHANES 1999-2002. Twelve and 31 associations were identified in the Marshfield samples at p<0.01 and p<0.05, respectively. Seven and 13 measures replicated in at least one of the NHANES at p<0.01 and p<0.05, respectively, with the same direction of effect. The most significant environmental exposures associated with T2D status included decreased alcohol use as well as increased smoking exposure in childhood and adulthood. The results demonstrate the utility of the EWAS method and survey tools for identifying environmental components of complex diseases like type 2 diabetes. These high-throughput and comprehensive investigation methods can easily be applied to investigate the relation between environmental exposures and multiple phenotypes in future analyses.

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Geographical breakdown

Country Count As %
United States 1 1%
Unknown 76 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 15 19%
Student > Master 14 18%
Student > Ph. D. Student 12 16%
Student > Bachelor 7 9%
Professor 6 8%
Other 10 13%
Unknown 13 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 18%
Medicine and Dentistry 11 14%
Biochemistry, Genetics and Molecular Biology 9 12%
Computer Science 8 10%
Social Sciences 4 5%
Other 15 19%
Unknown 16 21%