Abstract
Background-Carotid intima-media thickness (CIMT) is a subclinical measure for atherosclerosis. Previously, we have mapped quantitative trait loci (QTLs) for CIMT to chromosomes 7p (maximum logarithm of odds=3.1) and to 14q (maximum logarithm of odds=2.3). We sought to identify the underlying genetic variants within those QTLs. Methods and Results-Using the 100 extended Dominican Republican (DR) families (N=1312) used in the original linkage study, we fine mapped the QTLs with 2031 tagging single nucleotide polymorphisms (SNPs). Promising SNPs in the family data set were examined in an independent population-based subcohort comprised of DR individuals (N=553) from the Northern Manhattan Study. Among the families, evidence for association (P<0.001) was found in multiple genes (ANLN, AOAH, FOXN3, CCDC88C, PRiMA1, and an intergenic SNP rs1667498), with the strongest association at PRiMA1 (P=0.00007, corrected P=0.047). Additional analyses revealed that the association at these loci, except PRiMA1, was highly significant (P=0.00004≈0.00092) in families with evidence for linkage, but not in the rest of families (P=0.13-0.80) and the population-based cohort, suggesting the genetic effects at these SNPs are limited to a subgroup of families. In contrast, the association at PRiMA1 was significant in both families with and without evidence for linkage (P=0.002 and 0.019, respectively) and the population-based subcohort (P=0.047), supporting a robust association. Conclusions-We identified several candidate genes for CIMT in DR families. Some of the genes manifest genetic effects within a specific subgroup and others were generalized to all groups. Future studies are needed to further evaluate the contribution of these genes to atherosclerosis.
| Original language | English |
|---|---|
| Pages (from-to) | 234-241 |
| Number of pages | 8 |
| Journal | Circulation: Cardiovascular Genetics |
| Volume | 5 |
| Issue number | 2 |
| DOIs | |
| State | Published - Apr 1 2012 |
Fingerprint
Keywords
- Atherosclerosis
- Carotid arteries
- Fine mapping
- Genetic association
- Quantitative trait locus mapping stroke
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Genetics(clinical)
- Genetics
Cite this
Fine mapping study reveals novel candidate genes for carotid intima-media thickness in dominican republican families. / Wang, Liyong; Beecham, Ashley; Zhuo, Degen; Dong, Chuanhui; Blanton, Susan H; Rundek, Tatjana; Sacco, Ralph L.
In: Circulation: Cardiovascular Genetics, Vol. 5, No. 2, 01.04.2012, p. 234-241.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fine mapping study reveals novel candidate genes for carotid intima-media thickness in dominican republican families
AU - Wang, Liyong
AU - Beecham, Ashley
AU - Zhuo, Degen
AU - Dong, Chuanhui
AU - Blanton, Susan H
AU - Rundek, Tatjana
AU - Sacco, Ralph L
PY - 2012/4/1
Y1 - 2012/4/1
N2 - Background-Carotid intima-media thickness (CIMT) is a subclinical measure for atherosclerosis. Previously, we have mapped quantitative trait loci (QTLs) for CIMT to chromosomes 7p (maximum logarithm of odds=3.1) and to 14q (maximum logarithm of odds=2.3). We sought to identify the underlying genetic variants within those QTLs. Methods and Results-Using the 100 extended Dominican Republican (DR) families (N=1312) used in the original linkage study, we fine mapped the QTLs with 2031 tagging single nucleotide polymorphisms (SNPs). Promising SNPs in the family data set were examined in an independent population-based subcohort comprised of DR individuals (N=553) from the Northern Manhattan Study. Among the families, evidence for association (P<0.001) was found in multiple genes (ANLN, AOAH, FOXN3, CCDC88C, PRiMA1, and an intergenic SNP rs1667498), with the strongest association at PRiMA1 (P=0.00007, corrected P=0.047). Additional analyses revealed that the association at these loci, except PRiMA1, was highly significant (P=0.00004≈0.00092) in families with evidence for linkage, but not in the rest of families (P=0.13-0.80) and the population-based cohort, suggesting the genetic effects at these SNPs are limited to a subgroup of families. In contrast, the association at PRiMA1 was significant in both families with and without evidence for linkage (P=0.002 and 0.019, respectively) and the population-based subcohort (P=0.047), supporting a robust association. Conclusions-We identified several candidate genes for CIMT in DR families. Some of the genes manifest genetic effects within a specific subgroup and others were generalized to all groups. Future studies are needed to further evaluate the contribution of these genes to atherosclerosis.
AB - Background-Carotid intima-media thickness (CIMT) is a subclinical measure for atherosclerosis. Previously, we have mapped quantitative trait loci (QTLs) for CIMT to chromosomes 7p (maximum logarithm of odds=3.1) and to 14q (maximum logarithm of odds=2.3). We sought to identify the underlying genetic variants within those QTLs. Methods and Results-Using the 100 extended Dominican Republican (DR) families (N=1312) used in the original linkage study, we fine mapped the QTLs with 2031 tagging single nucleotide polymorphisms (SNPs). Promising SNPs in the family data set were examined in an independent population-based subcohort comprised of DR individuals (N=553) from the Northern Manhattan Study. Among the families, evidence for association (P<0.001) was found in multiple genes (ANLN, AOAH, FOXN3, CCDC88C, PRiMA1, and an intergenic SNP rs1667498), with the strongest association at PRiMA1 (P=0.00007, corrected P=0.047). Additional analyses revealed that the association at these loci, except PRiMA1, was highly significant (P=0.00004≈0.00092) in families with evidence for linkage, but not in the rest of families (P=0.13-0.80) and the population-based cohort, suggesting the genetic effects at these SNPs are limited to a subgroup of families. In contrast, the association at PRiMA1 was significant in both families with and without evidence for linkage (P=0.002 and 0.019, respectively) and the population-based subcohort (P=0.047), supporting a robust association. Conclusions-We identified several candidate genes for CIMT in DR families. Some of the genes manifest genetic effects within a specific subgroup and others were generalized to all groups. Future studies are needed to further evaluate the contribution of these genes to atherosclerosis.
KW - Atherosclerosis
KW - Carotid arteries
KW - Fine mapping
KW - Genetic association
KW - Quantitative trait locus mapping stroke
UR - http://www.scopus.com/inward/record.url?scp=84860808246&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860808246&partnerID=8YFLogxK
U2 - 10.1161/CIRCGENETICS.111.961763
DO - 10.1161/CIRCGENETICS.111.961763
M3 - Article
C2 - 22423143
AN - SCOPUS:84860808246
VL - 5
SP - 234
EP - 241
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
SN - 1942-325X
IS - 2
ER -