Objective: Carotid plaque is a marker of subclinical atherosclerosis with a genetic component. The aim of this follow-up fine mapping study was to identify candidate genes for carotid plaque within four linkage regions. Methods: We successfully genotyped 3712 single nucleotide polymorphisms (SNPs) under the four linkage regions that were previously identified in 100 extended Dominican families. Family-based association tests were performed to investigate their associations with carotid plaque. Promising SNPs were evaluated in an independent population-based subcohort (N= 941, 384 Dominicans) from the Northern Manhattan Study (NOMAS). Results: In the family study, evidence for association (p< 0.0005) was found regarding several genes (NAV2, EFCAB11/TDP1, AGBL1, PTPN9, LINGO1 and LOC730118), with the strongest association at rs4143999 near EFCAB11/TDP1 (p= 0.00001 for carotid presence and 0.00003 for plaque area, multiple testing corrected p≤ 0.02). The association in AGBL1 and PTPN9 was mainly driven by the families with linkage evidence (p= 0.00008-0.00001 and 0.76-0.32, respectively, in the families with and without linkage evidence). However, these associations explained only a small portion of the observed linkage. In NOMAS, replication (p< 0.05 in the whole NOMAS subcohort and p< 0.10 in the smaller Dominican subcohort) was found for SNPs within/near EFCAB11, NAV2, AGBL1 and other genes. Conclusion: This follow-up study has identified multiple candidate genes for carotid plaque in the Dominican population. Many of these genes have been implicated in neurodegenerative and cardiovascular diseases. Further studies with in-depth re-sequencing are needed to uncover both rare and common functional variants that contribute to the susceptibility to atherosclerosis.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Jul 2012|
- Carotid plaque
- Fine mapping
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine