SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in african-americans of the GENOA study
dc.contributor.author | Meyers, Kristin J | |
dc.contributor.author | Chu, Jian | |
dc.contributor.author | Mosley, Thomas H | |
dc.contributor.author | Kardia, Sharon L | |
dc.date.accessioned | 2015-08-07T17:47:19Z | |
dc.date.available | 2015-08-07T17:47:19Z | |
dc.date.issued | 2010-11-10 | |
dc.identifier.citation | BMC Medical Genetics. 2010 Nov 10;11(1):160 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/112863 | en_US |
dc.description.abstract | Abstract 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. | |
dc.title | SNP-SNP interactions dominate the genetic architecture of candidate genes associated with left ventricular mass in african-americans of the GENOA study | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/112863/1/12881_2010_Article_721.pdf | |
dc.identifier.doi | 10.1186/1471-2350-11-160 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Meyers et al. | |
dc.date.updated | 2015-08-07T17:47:20Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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