Polygenic risk score and coronary artery disease: A meta-analysis of 979,286 participant data

被引：21

作者：

Agbaedeng, Thomas A. ^{[1
,2
]}

Noubiap, Jean Jacques ^{[1
]}

Mato, Edith Pascale Mofo ^{[3
]}

Chew, Derek P. ^{[4
,5
]}

Figtree, Gemma A. ^{[6
,7
]}

Said, M. Abdullah ^{[8
]}

van der Harst, Pim ^{[9
]}

机构：

[1] Univ Adelaide, Ctr Heart Rhythm Disorders, Adelaide, SA, Australia

[2] Ctr Cardiometab Expt & Innovat, Adelaide, SA, Australia

[3] Univ Kwazulu Natal, Mol & Clin Pharmacol Res Lab, Durban, South Africa

[4] Flinders Univ S Australia, Coll Med & Publ Hlth, Adelaide, SA, Australia

[5] South Australian Hlth & Med Res Inst, Heart Hlth Theme, Adelaide, SA, Australia

[6] Univ Sydney, Kolling Inst, Sydney, NSW, Australia

[7] Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia

[8] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-9700 RB Groningen, Netherlands

[9] Univ Med Ctr Utrecht, Dept Cardiol, Heart & Lung Div, Utrecht, Netherlands

来源：

ATHEROSCLEROSIS | 2021年 / 333卷

关键词：

Polygenic risk score; Coronary artery disease; Myocardial infarction; Genome-wide association study; Single-nucleotide polymorphism; GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; HEART-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; ACCURACY; PREDICTION; SEX;

D O I：

10.1016/j.atherosclerosis.2021.08.020

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aims: Coronary artery disease (CAD) is a complex disease with a strong genetic basis. While previous studies have combined common single-nucleotide polymorphisms (SNPs) into a polygenic risk score (PRS) to predict CAD risk, this association is poorly characterised. We performed a meta-analysis to estimate the effect of PRS on the risk of CAD. Methods: Online databases were searched for studies reporting PRS and CAD. PRS computation was based on logodds (PRSLN), pruning or clumping and thresholding (PRSP/C + T), Lassosum regression (PRSLassosum), LDpred (PRSLDpred), or metaGRS (PRSmetaGRS). The reported odds ratio (OR), hazard ratio (HR), C-indexes and their corresponding 95% confidence interval (95% CI) were pooled in a random-effects meta-analysis. Results: Forty-nine studies were included (979,286 individuals). There was a significant association between 1standard deviation [SD] increment in PRS and adjusted risks of both incident and prevalent CAD (OR [95% CI]: 1.67 [1.57-1.77] for PRSmetaGRS, 1.46 [1.26-1.68] for PRSLDpred). The risk of incident CAD was highest for PRSP/C + T (HR [95% CI]: 1.49 [1.26-1.78]), PRSmetaGRS (1.37 [1.27-1.47]), and PRSLDpred (1.36 [1.31-1.42]). Analysis of model performance demonstrated that PRS predicted incident CAD with C-index of up to 0.71. Importantly, addition of PRS to clinical risk scores resulted in modest but statistically significant improvements in CAD risk prediction, with 1.5% observed for PRSP/C + T (p < 0.001) and 1.6% for PRSLDpred (p < 0.001). Conclusions: Polygenic risk score is strongly associated with increased risks of CAD. Future prospective studies should explore the usefulness of polygenic risk scores for identifying individuals at a high risk of developing CAD.

引用

页码：48 / 55

页数：8

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