title: SNPs and other features as they predispose to complex disease: genome-wide predictive analysis of a quantitative phenotype for hypertension.
abstract: Though recently they have fallen into some disrepute, genome-wide association studies (GWAS) have been formulated and applied to understanding essential hypertension. The principal goal here is to use data gathered in a GWAS to gauge the extent to which SNPs and their interactions with other features can be combined to predict mean arterial blood pressure (MAP) in 3138 pre-menopausal and naturally post-menopausal white women. More precisely, we quantify the extent to which data as described permit prediction of MAP beyond what is possible from traditional risk factors such as blood cholesterol levels and glucose levels. Of course, these traditional risk factors are genetic, though typically not explicitly so. In all, there were 44 such risk factors/clinical variables measured and 377,790 single nucleotide polymorphisms (SNPs) genotyped. Data for women we studied are from first visit measurements taken as part of the Atherosclerotic Risk in Communities (ARIC) study. We begin by assessing non-SNP features in their abilities to predict MAP, employing a novel regression technique with two stages, first the discovery of main effects and next discovery of their interactions. The long list of SNPs genotyped is reduced to a manageable list for combining with non-SNP features in prediction. We adapted Efron's local false discovery rate to produce this reduced list. Selected non-SNP and SNP features and their interactions are used to predict MAP using adaptive linear regression. We quantify quality of prediction by an estimated coefficient of determination (R(2)). We compare the accuracy of prediction with and without information from SNPs.
authors.affiliation: VA Cooperative Studies Program, Mountain View, California, United States of America.
authors.forename: Joong-Ho
authors.initials: JH
authors.lastname: Won
authors.forename: Georg
authors.initials: G
authors.lastname: Ehret
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Richard A
authors.initials: RA
authors.lastname: Olshen
mesh_terms: D000368:Aged; D000465:Algorithms; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*