Polygenic Risk Score for Type 2 Diabetes

DNA was extracted from whole blood samples from 537 participants using a Maxiprep kit (Qiagen, Valencia, CA, USA). We genotyped 336 SNPs associated with type 2 diabetes, obesity or hyperlipidaemia using a Sequenom iPLEX platform (Sequenom, San Diego, CA, USA) in the year 2014.
We used PLINK 1.9 software (http://pngu.mgh.harvard.edu/~purcell/plink/) for genotype quality control and clumping [18 (link)]. We used the following parameters for clumping of the genotype data: p value threshold 1, linkage disequilibrium threshold (r²) 0.5, clumping window width 250 kb. Prior to clumping, we excluded all SNPs with a minor allele frequency <0.05, genotyping rate <0.9 and Hardy–Weinberg equilibrium p value <1 × 10⁻⁴. We also excluded samples if data on >10% of SNPs were missing. After quality control, there were 537 samples with genotype data on 195 SNPs. We used PRSice 2.1 [19 (link)] to calculate the PRS, using the genotype quality control settings recommended by the software developers [20 (link)]. For the SNP weights, we used the effect-size estimates obtained from Xue et al [21 (link)]. We applied a p value threshold of 5 × 10⁻⁸ for including type 2 diabetes-associated SNPs in the PRS. This resulted in inclusion of 50 SNPs in the PRS.