Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction.

Ganna A, Magnusson PK, Pedersen NL, de Faire U, Reilly M, Arnlöv J, Sundström J, Hamsten A, Ingelsson E.

Source

From the Department of Medical Epidemiology and Biostatistics (A.G., P.K.E.M., N.L.P., M.R.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna (A.H.), Karolinska Institutet, Stockholm, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory (A.G., J.Ä., E.I.) and Department of Medical Sciences, Cardiovascular Epidemiology (J.S.), Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden (J.Ä.); and Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom (E.I.).

Abstract

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="" 0.004="" 0.017="" 1="" 318="" 4.2="" 4.9="" a="" addition="" additional="" and="" at="" be="" beyond="" by="" chd-specific="" chd="" classification="" could="" discrimination="" established="" estimate="" event="" every="" factors.="" factors="" for="" genetic="" improved="" improvement="" in="" index="" intermediate="" measuring="" mgrs.="" mgrs="" modest="" net="" p="" people="" performed="" polygene="" reclassification="" risk="" saved="" score="" screened="" than="" that="" the="" to="" was="" we="" worse="">

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.