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Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2013 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 33, no 9, 2267-2272 p.Article in journal (Refereed) Published
Abstract [en]

Objective-Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. Approach and Results-We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P<0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P=0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Conclusions-Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.

Place, publisher, year, edition, pages
2013. Vol. 33, no 9, 2267-2272 p.
Keyword [en]
association studies, genetics, risk assessment, risk prediction, risk score
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-207498DOI: 10.1161/ATVBAHA.113.301218ISI: 000323320700032OAI: oai:DiVA.org:uu-207498DiVA: diva2:648912
Available from: 2013-09-17 Created: 2013-09-16 Last updated: 2016-01-25Bibliographically approved

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Sundström, JohanIngelsson, Erik
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Department of Medical SciencesScience for Life Laboratory, SciLifeLabCardiovascular epidemiology
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