title: PSEUDOMARKER: a powerful program for joint linkage and/or linkage disequilibrium analysis on mixtures of singletons and related individuals.
abstract: A decade ago, there was widespread enthusiasm for the prospects of genome-wide association studies to identify common variants related to common chronic diseases using samples of unrelated individuals from populations. Although technological advancements allow us to query more than a million SNPs across the genome at low cost, a disappointingly small fraction of the genetic portion of common disease etiology has been uncovered. This has led to the hypothesis that less frequent variants might be involved, stimulating a renaissance of the traditional approach of seeking genes using multiplex families from less diverse populations. However, by using the modern genotyping and sequencing technology, we can now look not just at linkage, but jointly at linkage and linkage disequilibrium (LD) in such samples. Software methods that can look simultaneously at linkage and LD in a powerful and robust manner have been lacking. Most algorithms cannot jointly analyze datasets involving families of varying structures in a statistically or computationally efficient manner. We have implemented previously proposed statistical algorithms in a user-friendly software package, PSEUDOMARKER. This paper is an announcement of this software package. We describe the motivation behind the approach, the statistical methods, and software, and we briefly demonstrate PSEUDOMARKER's advantages over other packages by example.
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki. tero.hiekkalinna @ helsinki.fi
authors.forename: Tero
authors.initials: T
authors.lastname: Hiekkalinna
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Schäffer
authors.forename: Brian
authors.initials: B
authors.lastname: Lambert
authors.forename: Petri
authors.initials: P
authors.lastname: Norrgrann
authors.forename: Harald H H
authors.initials: HH
authors.lastname: Göring
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Terwilliger
mesh_terms: D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods*; D005787:Gene Frequency; D008040:Genetic Linkage; D056426:Genetic Loci; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D012107:Research Design; D012984:Software