Premium
Is It Rare or Common?
Author(s) -
Adhikari Kaustubh,
AlChawa Taofik,
Ludwig Kerstin,
Mangold Elisabeth,
Laird Nan,
Lange Christoph
Publication year - 2012
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.21637
Subject(s) - linkage disequilibrium , genome wide association study , genetics , coalescent theory , biology , single nucleotide polymorphism , genetic association , snp , computational biology , snp array , gene , genotype , phylogenetic tree
Many genome‐wide association studies (GWAS) have signals with unknown etiology. This paper addresses the question—is such an association signal caused by rare or common variants that lead to increased disease risk? For a genomic region implicated by a GWAS, we use single nucleotide polymorphism (SNP) data in a case‐control setting to predict how many common or rare variants there are, using a Bayesian analysis. Our objective is to compute posterior probabilities for configurations of rare and/or common variants. We use an extension of coalescent trees—the ancestral recombination graphs—to model the genealogical history of the samples based on marker data. As we expect SNPs to be in linkage disequilibrium with common disease variants, we can expect the trees to reflect the type of variants. To demonstrate the application, we apply our method to candidate gene sequencing data from a German case‐control study on nonsyndromic cleft lip with or without cleft palate. Genet. Epidemiol. 36:419‐429, 2012. © 2012 Wiley Periodicals, Inc.