Identity informative SNP associations in the UK Biobank

Abstract

Single nucleotide polymorphisms (SNPs) are amenable to genotyping DNA from degraded, inhibited, and/or ancient substrates due to their relatively small amplicon size. Though they have clear advantages over traditional short tandem repeat (STR) typing for specific casework scenarios, the advances in massively parallel sequencing (MPS) have drastically increased the utility of this marker type. The biallelic nature of SNPs makes them individually less informative than STRs due to limited heterozygosity; however, in sufficiently large multiplexes, identity informative SNPs (iiSNPs) may produce combined random match probabilities comparable to STR typing. Multiple MPS library preparation kits now include iiSNPs and similar to STRs, these loci have been rigorously characterized during multiplex development. The relative accessibility of genome-wide association study (GWAS) summary statistics enables re-investigation of forensically relevant targets in high-quality datasets. Here, 4085 GWASs from the UK Biobank European datasets (UKB; 787 ≤ N ≤ 361,194) were mined for iiSNPs typed by the ForenSeq DNA Signature Prep Kit (Verogen). Seven iiSNPs had genome-wide association (p ≤ 5 × 10−8) with 17 phenotypes in UKB Europeans. Most notably, these relationships involve two outwardly visible characteristics: standing height (rs907100; β = 0.011, p = 1.35 × 10-10) and hair/balding patterns (rs2399332; β = −0.009, p = 3.83 × 10−8). The remaining associations involve red blood cell characteristics and measures of lung function. Though these traits are highly polygenic and the individual SNP effects described here have been refuted empirically, we describe the importance and ease of exploring high-quality, freely accessible data to continuously and robustly characterize new and existing forensically relevant loci.