Assessment of the value of a genetic risk score in improving the estimation of coronary risk

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• 作者：Carla Lluis-Ganella^a ; ¹ ; Isaac Subirana^b ; ^a ; ¹ ; Gavin Lucas^a ; Marta Tomá ; s^a ; Daniel Muñ ; oz^a ; Mariano Sentí ; ^a ; ^c ; Eduardo Salas^d ; Joan Sala^e ; Rafel Ramos^f ; ^g ; Jose M. Ordovas^h ; ⁱ ; Jaume Marrugat^a ; Roberto Elosua^a ; ^b ; ^{relosua@imim.es}
• 关键词：AHA ; American Heart Association ; CHD ; coronary heart disease ; CVD ; Cardiovascular diseases ; CVRFs ; cardiovascular risk factors ; DNA ; deoxyribonucleic Acid ; GRS ; genetic risk score ; GWAS ; genome-wide association studies ; IDI ; integrated discrimination impr
• 刊名：Atherosclerosis
• 出版年：2012
• 期刊代码：28_00219150
• 类别：med
• 出版时间：June, 2012
• 卷：222
• 期：2
• 页码：456-463
• 文件大小：512 K

摘要

Background

The American Heart Association has established criteria for the evaluation of novel markers of cardiovascular risk. In accordance with these criteria, we assessed the association between a multi-locus genetic risk score (GRS) and incident coronary heart disease (CHD), and evaluated whether this GRS improves the predictive capacity of the Framingham risk function.

Methods and results

Using eight genetic variants associated with CHD but not with classical cardiovascular risk factors (CVRFs), we generated a multi-locus GRS, and found it to be linearly associated with CHD in two population based cohorts: The REGICOR Study (n = 2351) and The Framingham Heart Study (n = 3537) (meta-analyzed HR [95%CI]: 鈭?.13 [1.01-1.27], per unit). Inclusion of the GRS in the Framingham risk function improved its discriminative capacity in the Framingham sample (c-statistic: 72.81 vs.72.37, p = 0.042) but not in the REGICOR sample. According to both the net reclassification improvement (NRI) index and the integrated discrimination index (IDI), the GRS improved re-classification among individuals with intermediate coronary risk (meta-analysis NRI [95%CI]: 17.44 [8.04; 26.83]), but not overall.

Conclusions

A multi-locus GRS based on genetic variants unrelated to CVRFs was associated with a linear increase in risk of CHD events in two distinct populations. This GRS improves risk reclassification particularly in the population at intermediate coronary risk. These results indicate the potential value of the inclusion of genetic information in classical functions for risk assessment in the intermediate risk population group.