Abstract P260: Genome-wide Pathway and Network-based Approaches Identify Novel Genetic Loci and Pathways for Cardiovascular Disease and Diabetes in an Ethnically Diverse Cohort of American Women
Introduction: Despite the success of recent genome-wide association studies (GWAS) in identifying genetic loci associated with cardiovascular disease (CVD) and diabetes (T2D), a comprehensive examination of GWAS data for identifying biological pathways underlying their specific or shared genetic mechanisms is lacking, especially in an ethnicity-specific manner.
Hypothesis: We hypothesized that genetic variation clustered in biological pathways is associated with an increased risk of CVD and T2D.
Methods: We applied a pathway and network-based approach to characterize GWAS signals in sets of biological pathways for their contribution to CVD and T2D in two separate nation-wide populations of ethnically diverse women from the Women’s Health Initiative (WHI) Cohort, the WHI SNP Health Association Resource(WHI-SHARe) and the Genomics and Randomized Trials Network(WHI-GARNET), involving 8,155 African American, 3,494 Hispanic American, and 3,697 Caucasian American women.
Results: Eight pathways were identified to be significantly enriched for CVD, T2D, and combined CVD and T2D across the three ethnic groups at false discovery rate <0.001, including hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, calcium signaling pathway, axon guidance, cell adhesion molecules, focal adhesion, and ECM-receptor interaction pathways. We also identified disease- and ethnicity-specific pathways, such as cell cycle (specific for Hispanic and Caucasian Americans) and tight junction (CVD and combined CVD + T2D in Hispanic Americans).
Conclusions: By applying pathway- and network-based analyses to two large GWAS from three ethnic groups of American women, we identified shared biological pathways for CVD and T2D and disease- and ethnicity-specific pathways. These results provide evidence for multiple pathways underlying the pathogenesis of CVD and T2D in three genetically distinct populations and implicate the complex etiology of cardiometabolic disease.
Author Disclosures: K.K. Chan: None. Y. Huang: None. Y. Hsu: None. Y. Song: None. A. Hevener: None. Q. Meng: None. C. Wu: None. A. Reiner: None. E.M. Sobel: None. L. Tinker: None. X. Yang: None. S. Liu: None.
- © 2014 by American Heart Association, Inc.