Blood samples from participants at age 53 years were genotyped using MetaboChip, a custom Illumina iSelectarray (San Diego, CA, USA) that includes ~200,000 SNPs and covers the loci identified by genome-wide association studies (GWASs) in cardiometabolic diseases, including rare variants identified by the 1000 Genomes Project [27 (link)]. Quality control analysis of genotyped samples has been previously reported [28 (link)].
Three PRSs were calculated. A type 2 diabetes PRS has previously been derived for NSHD study members [29 (link)]. In brief, a genetic risk score was computed using the published coefficients for 65 SNPs identified by a prior GWAS for type 2 diabetes [30 (link), 31 ]. We additionally derived a PRS for insulin resistance using 17 previously demonstrated genome-wide significant SNPs [32 (link)] and for hyperglycaemia using ten previously demonstrated SNPs [32 (link)] using PRSice [33 (link)]. This calculates the sum of the number of risk alleles (unweighted score) carried by each person, and weights it based on previously published coefficients (weighted score). As is standard practice, SNPs with a minor allele frequency <0.01 were excluded.
Three PRSs were calculated. A type 2 diabetes PRS has previously been derived for NSHD study members [29 (link)]. In brief, a genetic risk score was computed using the published coefficients for 65 SNPs identified by a prior GWAS for type 2 diabetes [30 (link), 31 ]. We additionally derived a PRS for insulin resistance using 17 previously demonstrated genome-wide significant SNPs [32 (link)] and for hyperglycaemia using ten previously demonstrated SNPs [32 (link)] using PRSice [33 (link)]. This calculates the sum of the number of risk alleles (unweighted score) carried by each person, and weights it based on previously published coefficients (weighted score). As is standard practice, SNPs with a minor allele frequency <0.01 were excluded.
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