TY - JOUR
T1 - Polygenic risk score and coronary artery disease
T2 - A meta-analysis of 979,286 participant data
AU - Agbaedeng, Thomas A.
AU - Noubiap, Jean Jacques
AU - Mofo Mato, Edith Pascale
AU - Chew, Derek P.
AU - Figtree, Gemma A.
AU - Said, M. Abdullah
AU - van der Harst, Pim
PY - 2021/9
Y1 - 2021/9
N2 - 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 log-odds (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 1-standard 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.
AB - 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 log-odds (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 1-standard 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.
KW - Coronary artery disease
KW - Genome-wide association study
KW - Myocardial infarction
KW - Polygenic risk score
KW - Single-nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85113778382&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2021.08.020
DO - 10.1016/j.atherosclerosis.2021.08.020
M3 - Article
AN - SCOPUS:85113778382
SN - 0021-9150
VL - 333
SP - 48
EP - 55
JO - Atherosclerosis
JF - Atherosclerosis
ER -