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A combined genome-wide linkage and association approach to find susceptibility loci for platelet function phenotypes in European American and African American families with coronary artery disease
- Source :
- BMC Medical Genomics, BMC Medical Genomics, Vol 3, Iss 1, p 22 (2010)
- Publication Year :
- 2010
- Publisher :
- Springer Science and Business Media LLC, 2010.
-
Abstract
- Background The inability of aspirin (ASA) to adequately suppress platelet aggregation is associated with future risk of coronary artery disease (CAD). Heritability studies of agonist-induced platelet function phenotypes suggest that genetic variation may be responsible for ASA responsiveness. In this study, we leverage independent information from genome-wide linkage and association data to determine loci controlling platelet phenotypes before and after treatment with ASA. Methods Clinical data on 37 agonist-induced platelet function phenotypes were evaluated before and after a 2-week trial of ASA (81 mg/day) in 1231 European American and 846 African American healthy subjects with a family history of premature CAD. Principal component analysis was performed to minimize the number of independent factors underlying the covariance of these various phenotypes. Multi-point sib-pair based linkage analysis was performed using a microsatellite marker set, and single-SNP association tests were performed using markers from the Illumina 1 M genotyping chip from deCODE Genetics, Inc. All analyses were performed separately within each ethnic group. Results Several genomic regions appear to be linked to ASA response factors: a 10 cM region in African Americans on chromosome 5q11.2 had several STRs with suggestive (p-value < 7 × 10-4) and significant (p-value < 2 × 10-5) linkage to post aspirin platelet response to ADP, and ten additional factors had suggestive evidence for linkage (p-value < 7 × 10-4) to thirteen genomic regions. All but one of these factors were aspirin response variables. While the strength of genome-wide SNP association signals for factors showing evidence for linkage is limited, especially at the strict thresholds of genome-wide criteria (N = 9 SNPs for 11 factors), more signals were considered significant when the association signal was weighted by evidence for linkage (N = 30 SNPs). Conclusions Our study supports the hypothesis that platelet phenotypes in response to ASA likely have genetic control and the combined approach of linkage and association offers an alternative approach to prioritizing regions of interest for subsequent follow-up.
- Subjects :
- Adult
Blood Platelets
Male
lcsh:Internal medicine
lcsh:QH426-470
Genotype
Genetic Linkage
Single-nucleotide polymorphism
Genome-wide association study
Coronary Artery Disease
Biology
Polymorphism, Single Nucleotide
White People
Genetic linkage
Research article
Genetics
Humans
SNP
Genetic Predisposition to Disease
Genetics(clinical)
Platelet activation
lcsh:RC31-1245
Genetics (clinical)
Linkage (software)
Principal Component Analysis
Aspirin
Middle Aged
Heritability
Platelet Activation
Black or African American
lcsh:Genetics
Phenotype
Chromosomes, Human, Pair 5
Microsatellite
Female
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 17558794
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- BMC Medical Genomics
- Accession number :
- edsair.doi.dedup.....5ffb5220f0cfa4d30fe977813846f264