Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel

Abstract

BackgroundAccurate determination of genetic ancestry is of high interest for many areas such as biomedical research, personal genomics and forensics. It remains an important topic in genetic association studies, as it has been shown that population stratification, if not appropriately considered, can lead to false-positive and -negative results. While large association studies typically extract ancestry information from available genome-wide SNP genotypes, many important clinical data sets on rare phenotypes and historical collections assembled before the GWAS area are in need of a feasible method (i.e., ease of genotyping, small number of markers) to infer the geographic origin and potential admixture of the study subjects. Here we report on the development, application and limitations of a small, multiplexable ancestry informative marker (AIM) panel of SNPs (or AISNP) developed specifically for this purpose.ResultsBased on worldwide populations from the HGDP, a 41-AIM AISNP panel for multiplex application with the ABI SNPlex and a subset with 31 AIMs for the Sequenome iPLEX system were selected and found to be highly informative for inferring ancestry among the seven continental regions Africa, the Middle East, Europe, Central/South Asia, East Asia, the Americas and Oceania. The panel was found to be least informative for Eurasian populations, and additional AIMs for a higher resolution are suggested. A large reference set including over 4,000 subjects collected from 120 global populations was assembled to facilitate accurate ancestry determination. We show practical applications of this AIM panel, discuss its limitations for admixed individuals and suggest ways to incorporate ancestry information into genetic association studies.ConclusionWe demonstrated the utility of a small AISNP panel specifically developed to discern global ancestry. We believe that it will find wide application because of its feasibility and potential for a wide range of applications.

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

“…Imputations were performed using the default parameters in IMPUTE2 v2.2.2, using 1000 Genomes Phase 1 integrated variant set haplotypes for the autosomes and the interim set for the X chromosome (see Nievergelt et al, 2014 for details). In brief, prior to imputation, genetic markers that failed Hardy-Weinberg equilibrium (p < 5 × 10 −4 ), or had exceedingly rare alternative alleles (minor allele frequency MAF <0.005) were excluded.…”

“…Ancestry was determined using genetic information as described in Nievergelt et al (2013). In brief, genotypes of 1783 ancestry-informative markers (AIMs) were used to determine a subject's ancestry at the continental level for the 7 geographic regions Africa, Middle East, Europe, Central/South Asia, East Asia, Americas, and Oceania.…”

Circadian Polymorphisms in Night Owls, in Bipolars, and in Non-24-Hour Sleep Cycles

“…The final Illumina assay dataset for the Sleep-Center patients genotyped 630 SNPs (average call rate 99.7%). In addition, 41 SNPs selected as ancestry-informative markers (AIMs) were genotyped with Sequenom and SNPlex assays 42. Various polymorphisms including the PER3 VNTR (rs57875989) were explored with supplemental Taqman assays.…”

Inference of Ancestry in Forensic Analysis I: Autosomal Ancestry-Informative Marker Sets

“…Furthermore, the SNPs are combined into three separate multiplexes, although data from 32 AIM-SNPs can be applied separately for ancestry analysis (see listing in FROGkb) and the paper includes Snipper training sets for this purpose (US populations of: Europeans, African Americans, Hispanics, and East Asians) as supplementary fi les [ 20 ]. Lastly, the FROGkb website lists a set of 55 candidate AIM SNPs, of which 41 have been developed as iPLEX assays (the Sequenom spectrometric SBE-based genotyping system) described by Nievergelt et al [ 21 ]. The iPLEX assays would be easily adaptable to SNaPshot chemistry and these loci are likely to be of interest for laboratories aiming to build new ancestry tests or combine the best markers from each of four optimized forensic tests.…”