Gene expression signatures of coronary heart disease: The NHLBI SABRe CVD Initiative

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHLBI	EPID-9

Authors

• R Joehanes
• S Ying
• AD Johnson
• R Wang
• N Raghavachari
• CJ O'Donnell
• PJ Munson
• D Levy

Abstract

Recent research has indicated that coronary heart disease (CHD) is a complex condition influenced by the interaction of environment and largely unknown genetic factors of weak effect. More thorough studies are needed for new discoveries and to replicate previous findings. The primary goal of this study is to identify, validate, and characterize gene expression biomarkers of CHD from whole blood samples in a case-control design study within the offspring cohort of the Framingham Heart Study. This study focuses on three 190 CHD cases and 190 matched controls. Cases and controls were matched on age, sex, and statin therapy. Linear mixed effect models adjusted for additional CHD risk factors including cigarette smoking, hypertension, dyslipidemia, and diabetes. We found 29 genes associated with CVD at a false discovery rate < 0.5. Effect sizes, however were small (≤1.3 fold change in cases vs. controls). Gene-gene interactions and pathways analyses were conducted to elucidate the networks underlying CHD. In doing so we identified two cholesterol-transporter genes, ABCA6 and ABCA9, as network hubs. We conclude that due to small effect sizes of individual gene expression signals for CHD, network analysis is important in discovering novel genes involved in CHD.

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