Abstract 1878: Association of MYPT2 and Inflammatory Markers Using Principal Component Analysis in a Family-Based Genome-wide Association Study
Background: Vascular inflammation is a major mechanism leading to atherosclerosis. We performed a genome-wide association study to look for genes that influence individual latent inflammatory traits based on principal component analysis (PCA), as well as inflammatory marker levels.
Method: Hs-CRP, IL-6 and MCP-1 were measured in healthy members of families with early onset coronary artery disease (CAD). Latent inflammatory traits were constructed using PCA, and tested for genome-wide association in the Illumina HumanMap 1M SNP chip. SNPs were screened for association with individual markers and PCA traits adjusting for age and sex, using generalized estimating equations to adjust for family-relatedness. Population stratification was taken into account using EIGENSTRAT. Signals from screening with p-value < 10 –7 were verified with a computational-intensive family-based association test using MERLIN.
Result: PC1 represented a latent trait that loaded positively on CRP and IL-6, and PC2 represented mainly a latent trait loaded on MCP-1. Table 1⇓ shows the top five SNPs that passed genome-wide significance for PCA trait analysis, and Table 2⇓ shows the results for individual marker analysis - one intergenic SNP in chromosome 5, and four SNPs in the MYPT2 gene in chromosome 1.
Summary: We have shown that variants in MYPT2, which encodes a phosphatase widely expressed in heart and skeletal muscle, are associated with the inflammatory markers hs-CRP, IL-6 and MCP-1, with the strongest associations to CRP and to a principal component weighted heavily for CRP and IL-6. This gene may underlie pathologic inflammatory cascades resulting in myocyte or vascular dysfunction.