Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits

We aimed to identify common genetic variants affecting more than one of these traits using genome-wide association analysis in 2548 adolescents and 9145 adults from 4986 Australian twin families. Multivariate and univariate associations were performed.Multivariate analyses identified eight loci, and univariate association analyses confirmed two loci influencing more than one trait at p < 5 × 10-8. These are located on chromosome 8 (LPL gene affecting HDL and triglycerides) and chromosome 19 (TOMM40/APOE-C1-C2-C4 gene cluster affecting LDL and CRP). A locus on chromosome 12 (OASL gene) showed effects on GGT, LDL and CRP. The loci on chromosomes 12 and 19 unexpectedly affected LDL cholesterol and CRP in opposite directions.We identified three possible loci that may affect multiple traits and validated 17 previously-reported loci. Our study demonstrated the usefulness of examining multiple phenotypes jointly and highlights an anomalous effect on CRP, which is increasingly recognised as a marker of cardiovascular risk as well as of inflammation.Genome-wide association studies (GWAS) have become a major strategy for genetic dissection of human complex diseases. There is substantial overlap, both phenotypically and in allelic associations, between biomarkers and/or risk factors and between related diseases, and it is becoming important to understand the ways in which polymorphisms affect multiple phenotypes. Many phenotypes may be available from a single study population but current GWAS approaches usually examine them separately within a univariate framework. This strategy ignores potential genetic correlation between different traits.From the perspective of maximising power for a given size of dataset, it has been shown that joint analyses of correlated traits in linkage analysis have substantially improved power in localizing genes [1-4]. Similarly, multivariate approaches in association studies can theoretically improve the ability to detect genetic variants whose eff