Participants were genotyped using the Affymetrix 6.0 array (Affymetrix Inc, Santa Clara, CA, USA). Genotyped variants were used to impute to the TOPMed (version R2) reference panel. Haplotype phasing and imputation was performed using the Michigan Imputation Server,28 (link) which is available at https://imputationserver.sph.umich.edu .
A PRS for CHD, based on over six million genetic variants, was developed using the LDPred algorithm on individuals of European ancestry in UK Biobank by Khera et al.8 (link) Based on the publicly available weights from this published score, a PRS was created by multiplying the risk allele dosage with the weights. After restricting to single nucleotide polymorphisms (SNPs) with an imputation quality r2 greater than 0.3 in ARIC, 6,483,355 SNPs were included in an additive weighted genetic risk score calculated by summing the weighted dosages for each individual. A residual PRS was then created after adjusting for the first eleven principal components for ancestry. Individuals were further categorized into low (<20th percentile), intermediate (20th-80th percentile), and high (>80th percentile) genetic risk categories according to their self-reported race. To maximize the statistical precision and analyze the effects of low and high polygenic risk, the intermediate genetic risk category was used as the reference.
A PRS for CHD, based on over six million genetic variants, was developed using the LDPred algorithm on individuals of European ancestry in UK Biobank by Khera et al.8 (link) Based on the publicly available weights from this published score, a PRS was created by multiplying the risk allele dosage with the weights. After restricting to single nucleotide polymorphisms (SNPs) with an imputation quality r2 greater than 0.3 in ARIC, 6,483,355 SNPs were included in an additive weighted genetic risk score calculated by summing the weighted dosages for each individual. A residual PRS was then created after adjusting for the first eleven principal components for ancestry. Individuals were further categorized into low (<20th percentile), intermediate (20th-80th percentile), and high (>80th percentile) genetic risk categories according to their self-reported race. To maximize the statistical precision and analyze the effects of low and high polygenic risk, the intermediate genetic risk category was used as the reference.
