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GWAS-identified loci for coronary heart disease are associated with intima-media thickness and plaque presence at the carotid artery bulb
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0001-8081-428X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2015 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 239, no 2, 304-310 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Large-scale genome-wide association studies (GWAS) have so far identified 45 loci that are robustly associated with coronary heart disease (CHD) in data from adult men and women of European descent.

OBJECTIVES: To examine whether the CHD-associated loci are associated with measures of atherosclerosis in data from up to 9582 individuals of European ancestry.

METHODS: Forty-five SNPs representing the CHD-associated loci were genotyped in middle-aged to elderly individuals of European descent from four independent population-based studies (IMPROVE, MDC-CC, ULSAM and PIVUS). Intima-media thickness (IMT) was measured by external B-mode ultrasonography at the far wall of the bulb (sinus) and common carotid artery. Plaque presence was defined as a maximal IMT of the bulb >1.5 mm. We meta-analysed single-SNP associations across the four studies, and combined them in a genetic predisposition score. We subsequently examined the association of the genetic predisposition score with prevalent CHD and the three indices of atherosclerosis, adjusting for sex, age and Framingham risk factors.

RESULTS: As anticipated, the genetic predisposition score was associated with prevalent CHD, with each additional risk allele increasing the odds of disease by 5.5% (p = 4.1 × 10(-6)). Moreover, each additional CHD-risk allele across the 45 loci was associated with a 0.24% increase in IMT (p = 4.0 × 10(-3)), and with a 2.8% increased odds of plaque presence (p = 7.4 × 10(-6)) at the far wall of the bulb. The genetic predisposition score was not associated with IMT of the common carotid artery (p = 0.47).

CONCLUSIONS: Our results suggest that the association between the 45 previously identified loci and CHD at least partly acts through atherosclerosis.

Place, publisher, year, edition, pages
2015. Vol. 239, no 2, 304-310 p.
National Category
Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:uu:diva-244377DOI: 10.1016/j.atherosclerosis.2015.01.032ISI: 000351061600004PubMedID: 25682028OAI: oai:DiVA.org:uu-244377DiVA: diva2:788659
Available from: 2015-02-16 Created: 2015-02-16 Last updated: 2017-12-04Bibliographically approved

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den Hoed, MarcelGustafsson, StefanAxelsson, TomasSyvänen, Ann-ChristineIngelsson, ErikLind, Lars

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den Hoed, MarcelGustafsson, StefanAxelsson, TomasSyvänen, Ann-ChristineIngelsson, ErikLind, Lars
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Molecular epidemiologyScience for Life Laboratory, SciLifeLabDepartment of Medical SciencesMolecular MedicineCardiovascular epidemiology
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Atherosclerosis
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