Capability of common SNPs to tag rare variants

Xiangqing Sun,Robert C Elston,Junghyun Namkung,Xiaofeng Zhu

doi:10.1186/1753-6561-5-s9-s88

Abstract

Genome-wide association studies are based on the linkage disequilibrium pattern between common tagging single-nucleotide polymorphisms (SNPs) (i.e., SNPs having only common alleles) and true causal variants, and association studies with rare SNP alleles aim to detect rare causal variants. To better understand and explain the findings from both types of studies and to provide clues to improve the power of an association study with only common SNPs genotyped, we study the correlation between common SNPs and the presence of rare alleles within a region in the genome and look at the capability of common SNPs in strong linkage disequilibrium with each other to capture single rare alleles. Our results indicate that common SNPs can, to some extent, tag the presence of rare alleles and that including SNPs in strong linkage disequilibrium with each other among the tagging SNPs helps to detect rare alleles.

Highlights

In recent years, genome-wide association studies have identified hundreds of genetic variants that may be associated with many common diseases [1,2,3]
It is believed that the associated single-nucleotide polymorphisms (SNPs) detected from current association studies may represent linkage disequilibrium (LD) between a common tagging SNP and true causal variants
For the second question, we studied the change in correlation between a single rare SNP and common tagging SNPs that is achieved by including SNPs in strong LD with each other when selecting common tagging SNPs

Summary

Introduction

Genome-wide association studies have identified hundreds of genetic variants that may be associated with many common diseases [1,2,3]. We try to answer two questions: (1) Within a region in the genome, how well do common SNPs tag the presence of rare alleles? (2) When selecting common tagging SNPs for association studies to detect rare alleles, should we exclude SNPs in strong LD with each other (r2 > 0.95), or does it help to capture more information on the rare alleles if we include tagging SNPs in strong LD (r2 > 0.95) with each other? To answer the first question, we analyzed the correlation between common SNPs and the number of rare alleles in samples of rare SNPs (i.e., SNPs containing rare alleles) in each region of the chromosomes. For the second question, we studied the change in correlation between a single rare SNP and common tagging SNPs that is achieved by including SNPs in strong LD with each other when selecting common tagging SNPs

Methods

Results

Conclusion