A method to assess linkage disequilibrium between CNVs and SNPs inside copy number variable regions

Abstract

Since the discovery ofthe ubiquitous contribution of copy number variation to genetic variability, researchers have commonly used metrics such as r2 to quantify linkage disequilibrium (LD) between copy numbervariants (CNVs) and single nucleotide polymorphisms (SNPs). However, these reports have been restricted to SNPs outside copy number variable regions (CNVR) as current methods have not been adapted to account for SNPs displaying variable copy number. We show that traditional LD metrics inappropriately quantify SNP/CNVcovariance when SNPs lie within CNVR. We derive a new method for measuring LD that solves this issue, and defaults to traditional metrics otherwise. Finally, we present a procedure to estimate CNV-SNP allele frequencies from unphased CNV-SNP genotypes. Our method allows researchers to include all SNPs in SNP/CNV LD measurements, regardless of copy number. © 2011 Wineinger, Pajewski and Tiwari.