Genotyping and Imputation for Telomere Length

Genomic DNA was isolated from peripheral blood using the QIAamp blood DNA extraction kit (Qiagen, Valencia, CA, USA). All the genotyping was done in the Genotyping Core of MD Anderson Cancer Center using Illumina’s Infinium OncoArray-500K Beadchip. Genome Studio software (Illumina, San Diego, CA, USA) was utilized to analyze the genotyping data. The mean concordance rate of 2% replicated samples was 99.2%. We removed nonconcordant SNPs for analyses. All the samples had an overall SNP call rate >95%. Individual SNPs with minor allele frequency (MAF) <1% and call rate <90% were excluded for analysis. Imputation was performed using the Michigan Imputation Server (https://imputationserver.sph.umich.edu/), an online server that generates phased and imputed genotypes using the Haplotype Reference Consortium (HRC Version r1.1) reference panels [64 (link)]. Eleven independent SNPs were associated with LTL by large scale GWAS [40 (link),41 (link),42 (link)] and were used to construct a genetic risk score (GRS). Among these SNPs, four SNPs (rs10936599, rs2736100, rs9420907, and rs755017) were directly genotyped on OncoArray-500K, and the other seven were imputed with a high imputation accuracy (mean R²) of 0.96.