Results of tests of association with ECB21 for all SNPs in the non-Hispanic White subjects

<p><b>Copyright information:</b></p><p>Taken from "Application of the regression of offspring on mid-parent method to detect associations between single-nucleotide polymorphisms and the beta 2 electroencephalogram phenotype in the COGA data"</p><p></p><p>BMC Genetics 2005;6(Suppl 1):S56-S56.</p><p>Published online 30 Dec 2005</p><p>PMCID:PMC1866727.</p><p></p

Targeted deep sequencing of the <i>PEAR1</i> locus for platelet aggregation in European and African American families

<p>Coronary artery disease (CAD) remains a major cause of mortality and morbidity worldwide. The aggregation of activated platelets on a ruptured atherosclerotic plaque is a critical step in most acute cardiovascular events like myocardial infarction. Platelet aggregation both at baseline and after aspirin is highly heritable. Genome-wide association studies (GWAS) have identified a common variant within the first intron of the platelet endothelial aggregation receptor1 (<i>PEAR1</i>), to be robustly associated with platelet aggregation. In this study, we used targeted deep sequencing to fine-map the prior GWAS peak and identify additional rare variants of <i>PEAR1</i> that account for missing heritability in platelet aggregation within the GeneSTAR families.</p> <p>In this study, 1709 subjects (1043 European Americans, EA and 666 African Americans, AA) from families in the GeneSTAR study were included. In vitro platelet aggregation in response to collagen, ADP and epinephrine was measured at baseline and 14 days after aspirin therapy (81 mg/day). Targeted deep sequencing of <i>PEAR1</i> in addition to 2kb of upstream and downstream of the gene was performed. Under an additive genetic model, the association of single variants of <i>PEAR1</i> with platelet aggregation phenotypes were examined. Additionally, we examined the association between the burden of <i>PEAR1</i> rare non-synonymous variants and platelet aggregation phenotypes.</p> <p>Of 532 variants identified through sequencing, the intron 1 variant, rs12041331, was significantly associated with all platelet aggregation phenotypes at baseline and after platelet inhibition with aspirin therapy. rs12566888, which is in linkage disequilibrium with rs12041331, was associated with platelet aggregation phenotypes but to a lesser extent. In the EA families, the burden of <i>PEAR1</i> missense variants was associated with platelet aggregation after aspirin therapy when the platelets were stimulated with epinephrine (p = 0.0009) and collagen (p = 0.03). In AAs, the burden of <i>PEAR1</i> missense variants was associated, to a lesser degree, with platelet aggregation in response to epinephrine (p = 0.02) and ADP (p = 0.04).</p> <p>Our study confirmed that the GWAS-identified variant, rs12041331, is the strongest variant associated with platelet aggregation both at baseline and after aspirin therapy in our GeneSTAR families in both races. We identified additional association of rare missense variants in <i>PEAR1</i> with platelet aggregation following aspirin therapy. However, we observed a racial difference in the contribution of these rare variants to the platelet aggregation, most likely due to higher residual missing heritability of platelet aggregation after accounting for rs12041331 in the EAs compared to AAs.</p

Identification of tag single-nucleotide polymorphisms in regions with varying linkage disequilibrium-0

<p><b>Copyright information:</b></p><p>Taken from "Identification of tag single-nucleotide polymorphisms in regions with varying linkage disequilibrium"</p><p></p><p>BMC Genetics 2005;6(Suppl 1):S73-S73.</p><p>Published online 30 Dec 2005</p><p>PMCID:PMC1866708.</p><p></p>ith strong confidence. Light blue regions are D' = 1.0 but decreased confidence. White regions are D' < 1 and state D' within the box. An X denotes that SNP was selected by the program. The gray shading in the HAPLOVIEW row represents the Gabriel blocks. The dark lines represent breaks between blocks for both HAPLOVIEW and HaploBlock Finder. For some chromosomes no blocks were identified and this is indicated by hatch marks across the SNPs