Publication Date:
2010-11-10
Description:
Background Left ventricular mass (LVM) is a strong, independent predictor of heart disease incidence and mortality. LVM is a complex, quantitative trait with genetic and environmental risk factors. This research characterizes the genetic architecture of LVM in an African-American population by examining the main and interactive effects of individual candidate gene single nucleotide polymorphisms (SNPs) and conventional risk factors for increased LVM. Methods We used least-squares linear regression to investigate 1,878 SNPs from 234 candidate genes for SNP main effects, SNP-risk factor interactions, or SNP-SNP interactions associated with LVM in 1,328 African-Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We reduced the probability of false positive results by implementing three analytic criteria: 1) the false discovery rate, 2) cross-validation, and 3) testing for internal replication of results. Results We identified 409 SNP-SNP interactions passing all three criteria, while no SNP main effects or SNP-risk factor interactions passed all three. A multivariable model including four SNP-SNP interactions explained 11.3% of the variation in LVM in the full GENOA sample and 5.6% of LVM variation in independent test sets. Conclusions The results of this research underscore that context dependent effects, specifically SNP-SNP interactions, may dominate genetic contributions to variation in complex traits such as LVM.
Electronic ISSN:
1471-2350
Topics:
Biology
,
Medicine
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