PCA-Correlated SNPs for Structure Identification in Worldwide Human Populations

Abstract

Existing methods to ascertain small sets of markers for the identification of human population structure require prior knowledge of individual ancestry. Based on Principal Components Analysis (PCA), and recent results in theoretical computer science, we present a novel algorithm that, applied on genomewide data, selects small subsets of SNPs (PCA-correlated SNPs) to reproduce the structure found by PCA on the complete dataset, without use of ancestry information. Evaluating our method on a previously described dataset (10,805 SNPs, 11 populations), we demonstrate that a very small set of PCA-correlated SNPs can be effectively employed to assign individuals to particular continents or populations, using a simple clustering algorithm. We validate our methods on the HapMap populations and achieve perfect intercontinental differentiation with 14 PCA-correlated SNPs. The Chinese and Japanese populations can be easily differentiated using less than 100 PCA-correlated SNPs ascertained after evaluating 1.7 million SNPs from HapMap. We show that, in general, structure informative SNPs are not portable across geographic regions. However, we manage to identify a general set of 50 PCA-correlated SNPs that effectively assigns individuals to one of nine different populations. Compared to analysis with the measure of informativeness, our methods, although unsupervised, achieved similar results. We proceed to demonstrate that our algorithm can be effectively used for the analysis of admixed populations without having to trace the origin of individuals. Analyzing a Puerto Rican dataset (192 individuals, 7,257 SNPs), we show that PCA-correlated SNPs can be used to successfully predict structure and ancestry proportions. We subsequently validate these SNPs for structure identification in an independent Puerto Rican dataset. The algorithm that we introduce runs in seconds and can be easily applied on large genome-wide datasets, facilitating the identification of population substructure, stratification assessment in multi-stage whole-genome association studies, and the study of demographic history in human populations.

Author Summary

Genetic markers can be used to infer population structure, a task that remains a central challenge in many areas of genetics such as population genetics, and the search for susceptibility genes for common disorders. In such settings, it is often desirable to reduce the number of markers needed for structure identification. Existing methods to identify structure informative markers demand prior knowledge of the membership of the studied individuals to predefined populations. In this paper, based on the properties of a powerful dimensionality reduction technique (Principal Components Analysis), we develop a novel algorithm that does not depend on any prior assumptions and can be used to identify a small set of structure informative markers. Our method is very fast even when applied to datasets of hundreds of individuals and millions of markers. We evaluate this method on a large dataset of 11 populations from around the world, as well as data from the HapMap project. We show that, in most cases, we can achieve 99% genotyping savings while at the same time recovering the structure of the studied populations. Finally, we show that our algorithm can also be successfully applied for the identification of structure informative markers when studying populations of complex ancestry.