Abstract
While genome-wide linkage studies have been successful in mapping variants underlying rare monogenic disorders, genome-wide association studies may be more appropriate for detecting common variants of modest effects that underlie common disorders. To this end, we were interested in determining whether genetic variants associated with a phenotype differed depending on whether they were within or outside of regions linked to the phenotype. In particular, we compared allele frequencies and effect sizes between associated single-nucleotide polymorphisms within and outside of linkage regions using the Genetic Analysis Workshop 15 Problem 1. We did not find any statistically significant differences between these two sets. However, our power calculations show that these results may be inconclusive.
Highlights
Linkage analyses have proven effective for the identification of many traits that display a simple Mendelian inheritance pattern
We compared the distributions of allele frequencies and effect sizes between associated and linked single-nucleotide polymorphisms (SNPs) using data from the Genetic Analysis Workshop 15 (GAW15) Problem 1 and publicly available information from the HapMap project
For genome-wide linkage analyses, we obtained data from the GAW 15 Problem 1 data set, which included 3554 log2-transformed expression values and 2882 SNP genotypes for 14 Centre d'Etude du Polymorphisme Humain Utah (CEPH) families consisting of 194 individuals [2]
Summary
Linkage analyses have proven effective for the identification of many traits that display a simple Mendelian inheritance pattern These studies have been less successful in deciphering complex traits, potentially due to differing distributions of allele frequencies and effect sizes underlying these diseases across different populations. Linkage analysis can provide greater power to capture a rare variant with a large effect, whereas association studies may have greater power to detect common variants with small effects [1]. It remains unclear, whether associated variants will differ depending on whether they are within or outside of regions exhibiting linkage to the phenotype of interest. We evaluated the allele frequencies and estimated effect sizes of SNPs that are linked and/or associated with expression levels
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