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Assessment of genetic determinants of the association of ?' fibrinogen in relation to cardiovascular disease.

ABSTRACT: ?' fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of ?' fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort.A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for ?' fibrinogen levels from the cycle 7 examination. Fifty-four SNPs in or near the fibrinogen gene locus demonstrated genome-wide significance (P<5.0×10(-8)) for association with ?' fibrinogen levels. The top-signal SNP was rs7681423 (P=9.97×10(-110)) in the fibrinogen gene locus near FGG, which encodes the ? chain. Conditional on the top SNP, the only other SNP that remained genome-wide significant was rs1049636. Associations between SNPs, ?' fibrinogen levels, and prevalent CVD events were examined using multiple logistic regression. ?' fibrinogen levels were associated with prevalent CVD (P=0.02), although the top 2 SNPs associated with ?' fibrinogen levels were not associated with CVD. These findings contrast those for total fibrinogen levels, which are associated with different genetic loci, particularly FGB, which encodes the B? chain.?' fibrinogen is associated with prevalent CVD and with SNPs exclusively in and near the fibrinogen gene locus.

SUBMITTER: Lovely RS

PROVIDER: S-EPMC3174319 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Assessment of genetic determinants of the association of γ' fibrinogen in relation to cardiovascular disease.

Lovely Rehana S RS Yang Qiong Q Massaro Joseph M JM Wang Jing J D'Agostino Ralph B RB O'Donnell Christopher J CJ Shannon Jackilen J Farrell David H DH

Arteriosclerosis, thrombosis, and vascular biology 20110714 10

<h4>Objective</h4>γ' fibrinogen is a newly emerging biomarker that is associated with cardiovascular disease (CVD). However, the genetic determinants of γ' fibrinogen levels are unknown. We therefore conducted a genome-wide association study on 3042 participants from the Framingham Heart Study Offspring Cohort.<h4>Methods and results</h4>A genome-wide association study with 2.5 million single-nucleotide polymorphisms (SNPs) was carried out for γ' fibrinogen levels from the cycle 7 examination. F ...[more]

PMID: 21757653

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Project description:Migraine is associated with an increased risk for cardiovascular disease (CVD). Both migraine and CVD are highly heritable. However, the genetic liability for CVD among migraineurs is unclear.We performed a genome-wide association study for incident CVD events during 12 years of follow-up among 5,122 migraineurs participating in the population-based Women's Genome Health Study. Migraine was self-reported and CVD events were confirmed after medical records review. We calculated odds ratios (OR) and 95% confidence intervals (CI) and considered a genome-wide p-value <5×10(-8) as significant.Among the 5,122 women with migraine 164 incident CVD events occurred during follow-up. No SNP was associated with major CVD, ischemic stroke, myocardial infarction, or CVD death at the genome-wide level; however, five SNPs showed association with p<5×10(-6). Among migraineurs with aura rs7698623 in MEPE (OR?=?6.37; 95% CI 3.15-12.90; p?=?2.7×10(-7)) and rs4975709 in IRX4 (OR?=?5.06; 95% CI 2.66-9.62; p?=?7.7×10(-7)) appeared to be associated with ischemic stroke, rs2143678 located close to MDF1 with major CVD (OR?=?3.05; 95% CI 1.98-4.69; p?=?4.3×10(-7)), and the intergenic rs1406961 with CVD death (OR?=?12.33; 95% CI 4.62-32.87; p?=?5.2×10(-7)). Further, rs1047964 in BACE1 appeared to be associated with CVD death among women with any migraine (OR?=?4.67; 95% CI 2.53-8.62; p?=?8.0×10(-7)).Our results provide some suggestion for an association of five SNPs with CVD events among women with migraine; none of the results was genome-wide significant. Four associations appeared among migraineurs with aura, two of those with ischemic stroke. Although our population is among the largest with migraine and incident CVD information, these results must be treated with caution, given the limited number of CVD events among women with migraine and the low minor allele frequencies for three of the SNPs. Our results await independent replication and should be considered hypothesis generating for future research.

Dataset Information

Assessment of genetic determinants of the association of ?' fibrinogen in relation to cardiovascular disease.

Publications

Assessment of genetic determinants of the association of γ' fibrinogen in relation to cardiovascular disease.

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