Risk loci for coronary artery calcification replicated at 9p21 and 6q24 in the Heinz Nixdorf Recall StudyReport as inadecuate




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BMC Medical Genetics

, 14:23

Genetic epidemiology and genetic associations

Abstract

BackgroundAtherosclerosis is the primary cause of coronary heart disease CHD, preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms SNPs integrated on Metabochip and coronary artery calcification CAC, a valid risk factor for CHD, in an unselected, population-based German cohort.

MethodsThe Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants.

ResultsThe 9p21 variant, rs1537373, was most strongly associated Beta = 0.30; 95% confidence interval CI = 0.21-0.39; p = 4.05x10 with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, Beta = 0.30; 95% CI = 0.22-0.40; p = 4.67x10. Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC odds ratiors1537373 OR = 1.19; 95% CI = 1.07-1.31; p = 0.001 and ORrs9349379 = 1.26; 95% CI = 1.14-1.40; p = 1.5x10. Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC.

ConclusionWe demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries.

KeywordsCoronary heart disease Coronary artery calcification Cohort study Polymorphism Metabochip Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-14-23 contains supplementary material, which is available to authorized users.

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Author: Sonali Pechlivanis - Thomas W Mühleisen - Stefan Möhlenkamp - Dirk Schadendorf - Raimund Erbel - Karl-Heinz Jöckel - Per

Source: https://link.springer.com/







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