Abstract
We examined the clinical utility of two multi-locus genetic risk scores (GRSs) previously validated in Europeans among persons of African (AFR; n = 2,089), Latino (LAT; n = 4,349) and East-Asian (EA; n = 4,804) ancestry. We used data from the GERA cohort (30–79 years old, 68 to 73% female). We utilized two GRSs with 12 and 51 SNPs, respectively, and the Framingham Risk Score (FRS) to estimate 10-year CHD risk. After a median 8.7 years of follow-up, 450 incident CHD events were documented (95 in AFR, 316 in LAT and 39 EA, respectively). In a model adjusting for principal components and risk factors, tertile 3 vs. tertile 1 of GRS_12 was associated with 1.86 (95% CI, 1.15–3.01), 1.52 (95% CI, 1.02–2.25) and 1.19 (95% CI, 0.77–1.83) increased hazard of CHD in AFR, LAT and EA, respectively. Inclusion of the GRSs in models containing the FRS did not increase the C-statistic but resulted in net overall reclassification of 10% of AFR, 7% LAT and EA and in reclassification of 13% of AFR and EA as well as 10% LAT in the intermediate FRS risk subset. Our results support the usefulness of incorporating genetic information into risk assessment for primary prevention among minority subjects in the U.S.
Highlights
This study extends our prior report examining the utility of multi-locus genetic risk scores (GRSs) in CHD risk stratification among subjects of European ancestry in the GERA cohort[2] to participants of African-American, Latino and East Asian ancestry
As noted in the European sample, a weighted GRS consisting of 12 autosomal genetic variants was significantly associated with incident CHD independently of risk factors and self-reported family history of heart disease among African-Americans and Latinos, but not among East Asians
In the meta-analysis adjusting for genetic diversity (PCs), risk factors and combining all three minority groups, subjects in the top tertile of GRS_12 had a 48 percent increased risk of CHD compared to subjects in the bottom tertile
Summary
Received: 15 January 2018 Accepted: 22 March 2018 Published: xx xx xxxx of African, Latino and East-Asian Ancestry. We examined the clinical utility of two multi-locus genetic risk scores (GRSs) previously validated in Europeans among persons of African (AFR; n = 2,089), Latino (LAT; n = 4,349) and East-Asian (EA; n = 4,804) ancestry. We published a study showing improvement of the predictive capacity of the Framingham Risk Score after inclusion of four multi-locus genetic risk scores with increasing number of single nucleotide polymorphism (SNPs, namely GRS_8, GRS_12, GRS_36 and GRS_51) for incident coronary heart disease (CHD) among subjects of European ancestry in the Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort[2]. We expand the prior investigation by reporting the CHD predictive performance of GRS_12 and GRS_51 among persons of African (AFR), Latino (LAT) and East-Asian (EA) ancestry in the GERA cohort. Since results for GRS_8 were similar to GRS_12 and results for GRS-36 were similar to GRS_51, we focused on GRS_12 and GRS_51
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