Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation in individuals at high risk for coronary artery disease

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NHGRI	GEN/GENOM-9

* FARE Award Winner

Authors

• Y Kim
• RA Mathias
• N Faraday
• D Becker
• L Becker
• AF Wilson

Abstract

The Genetic Study of Aspirin Responsiveness is designed to examine genetic determinants of platelet aggregation in African American (AA) and European American (EA) healthy subjects with a family history of CAD. A previous GWAS detected a common genetic variant in intronic platelet endothelial aggregation receptor1 (PEAR1) gene. We exploit sequencing approach to identify additional functional variants in PEAR1. 104 subjects were selected based on the hyper and hypo aggregation across three different platelet agonists (Collagen, Epinephrine, and ADP). A 0.3Mb target including PEAR1 was Sanger sequenced at deCODE Genetics. Single-variant tests for association were performed using Fisher’s Exact Test. Collapsed multi-variant tests for association were performed after collapsing variants based on: minor allele frequency and predicted function. Out of 235 variants, more rare variants were noted in AAs compared to EAs. The common intronic GWAS-identified variant has the most significant association signal in AA; no additional association was seen for exonic variants. On the other hand, collapsed multi-variant tests suggest that exonic variants play a more significant role in EA. We confirm that a common intronic variant has the strongest association in AAs, and show that additional exonic variants play a role in platelet aggregation in EAs.

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