title: Is it rare or common?
abstract: 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.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. kadhikar.hsph@gmail.com
authors.forename: Kaustubh
authors.initials: K
authors.lastname: Adhikari
authors.forename: Taofik
authors.initials: T
authors.lastname: AlChawa
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ludwig
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Nan
authors.initials: N
authors.lastname: Laird
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D001499:Bayes Theorem; D016022:Case-Control Studies; D005819:Genetic Markers; D014644:Genetic Variation; D005858:Germany; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D017720:Molecular Epidemiology / Q000379:methods*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012306:Risk
chemical_list: D005819:Genetic Markers