期刊
EUROPEAN HEART JOURNAL
卷 37, 期 6, 页码 561-567出版社
OXFORD UNIV PRESS
DOI: 10.1093/eurheartj/ehv462
关键词
Coronary heart disease risk; Genetic risk scores
资金
- Swedish Cancer Society
- Swedish Medical Research Council
- Swedish Dairy Association
- Albert Pahlsson Foundation
- Gunnar Nilsson Foundation
- Malmo city council
- Japanese Circulation Society
- Massachusetts General Hospital (MGH)
- Howard Goodman Fellowship from MGH
- Donovan Family Foundation
- European Research Council [StG-282255]
- Swedish Heart and Lung Foundation
- Swedish Research Council
- Novo Nordisk Foundation
- Skane University Hospital donation funds
- Medical Faculty, Lund University
- Albert Pahlsson Research Foundation
- Region Skane
- King Gustav V and Queen Victoria Foundation
- Marianne and Marcus Wallenberg Foundation
- Quest Diagnostics
- Novo Nordisk Fonden [NNF14OC0009819, NNF13OC0005339] Funding Source: researchfish
Aims Genetic risk scores (GRSs) have been associated with coronary heart disease (CHD) in large studies. We asked whether expanding an established 27-variant GRS (GRS27) to a 50-variant GRS (GRS50) improved CHD prediction and whether GRSs are independent of self-reported family history of CHD. Methods and results The association between GRSs and incident CHD was assessed in Cox models adjusting for established risk factors in 23 595 participants of the Malmo Diet and Cancer study-a prospective, population-based study. During a median follow-up of 14.4 years, 2213 participants experienced a first CHD event. After adjustment for established risk factors, both GRS27 and GRS50 were associated with incident CHD [hazard ratio (HR) = 1.70 for high (top quintile) vs. low (bottom quintile) of GRS27; 95% confidence interval (CI): 1.48-1.94; P-trend = 1.6 x 10(-15) and HR = 1.92 for GRS50; 95% CI: 1.67-2.20; P-trend = 6.2 x 10(-22)]. Adding 23 single nucleotide polymorphisms (SNPs) to GRS27 improved risk prediction (P x 3 x 10(-6)). Further adjustment for self-reported family history did not appreciably change the risk estimates of either GRS27 (HR = 1.65; 95% CI: 1.45-1.89) or GRS50 (HR = 1.87; 95% CI: 1.63-2.14). The addition of GRS50 to established risk factors, including self-reported family history, improved discrimination (P<0.0001) and reclassification (continuous net reclassification improvement index = 0.17, P<0.0001). In young participants (below median age), those with high GRS50 had 2.4-fold greater risk (95% CI: 1.85-3.12) than those with low GRS50. Conclusion The addition of 23 SNPs to an existing GRS27 improved CHD risk prediction and was independent of self-reported family history. Coronary heart disease risk assessment by GRS could be particularly useful in young individuals.
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