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The Genetic Analysis Workshop 14 simulated data presents an interesting, challenging, and plausible example of a complex disease interaction in a dataset. This paper summarizes the ease of detection for each of the simulated Kofendrerd Personality Disorder (KPD) genes across all of the replicates for five standard linkage statistics. Using the KPD affection status, we have analyzed the microsatellite markers flanking each of the disease genes, plus an additional 2 markers that were not linked to any of the disease loci. All markers were analyzed using the following two-point linkage methods: 1) a MMLS, which is a standard admixture LOD score maximized over θ, α, and mode of inheritance, 2) a MLS calculated by GENEHUNTER, 3) the Kong and Cox LOD score as computed by MERLIN, 4) a MOD score (standard heterogeneity LOD maximized over θ, α, and a grid of genetic model parameters), and 5) the PPL, a Bayesian statistic that directly measures the strength of evidence for linkage to a marker. All of the major loci (D1–D4) were detectable with varying probabilities in the different populations. However, the modifier genes (D5 and D6) were difficult to detect, with similar distributions under the null and alternative across populations and statistics. The pooling of the four datasets in each replicate (n = 350 pedigrees) greatly improved the chance of detecting the major genes using all five methods, but failed to increase the chance to detect D5 and D6.

Mapping markers from linkage data continues to be a task performed in many genetic epidemiological studies. Data collected in a study may be used to refine published map estimates and a study may use markers that do not appear in any published map. Furthermore, inaccuracies in meiotic maps can seriously bias linkage findings. To make best use of the available marker information, multilocus linkage analyses are performed. However, two computational issues greatly limit the number of markers currently mapped jointly; the number of candidate marker orders increases exponentially with marker number and computing exact multilocus likelihoods on general pedigrees is computationally demanding. In this article, a new Markov chain Monte Carlo (MCMC) approach that solves both these computational problems is presented. The MCMC approach allows many markers to be mapped jointly, using data observed on general pedigrees with unobserved individuals. The performance of the new mapping procedure is demonstrated through the analysis of simulated an d real data. The MCMC procedure performs extremely well, even when there are millions of candidate orders, and gives results superior to those of CRI-MAP.

Motivation We present Eagle, a new method for multi-locus association mapping. The motivation for developing Eagle was to make multi-locus association mapping 'easy' and the method-of-choice. Eagle's strengths are that it (i) is considerably more powerful than single-locus association mapping, (ii) does not suffer from multiple testing issues, (iii) gives results that are immediately interpretable and (iv) has a computational footprint comparable to single-locus association mapping. Results By conducting a large simulation study, we will show that Eagle finds true and avoids false single-nucleotide polymorphism trait associations better than competing single- and multi-locus methods. We also analyze data from a published mouse study. Eagle found over 50% more validated findings than the state-of-the-art single-locus method. Availability and implementation Eagle has been implemented as an R package, with a browser-based Graphical User Interface for users less familiar with R. It is freely available via the CRAN website at https://cran.r-project.org. Videos, Quick Start guides, FAQs and Demos are available via the Eagle website http://eagle.r-forge.r-project.org. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

There is a growing need for the development of statistical techniques capable of mapping quantitative trait loci (QTL) in general outbred animal populations. Presently used variance component methods, which correctly account for the complex relationships that may exist between individuals, are challenged by the difficulties incurred through unknown marker genotypes, inbred individuals, partially or unknown marker phases, and multigenerational data. In this article, a two-step variance component approach that enables practitioners to routinely map QTL in populations with the aforementioned difficulties is explored. The performance of the QTL mapping methodology is assessed via its application to simulated data. The capacity of the technique to accurately estimate parameters is examined for a range of scenarios.

Eagle is an R package for multi-locus association mapping on a genome-wide scale. It is unlike other multi-locus packages in that it is easy to use for R users and non-users alike. It has two modes of use, command line and graphical user interface. Eagle is fully documented and has its own supporting website, http://eagle.r-forge.r-project.org/index.html. Eagle is a significant improvement over the method-of-choice, single-locus association mapping. It has greater power to detect SNP-trait associations. It is based on model selection, linear mixed models, and a clever idea on how random effects can be used to identify SNP-trait associations. Through an example with real mouse data, we demonstrate Eagle's ability to bring clarity and increased insight to single-locus findings. Initially, we see Eagle complementing single-locus analyses. However, over time, we hope the community will make, increasingly, multi-locus association mapping their method-of-choice for the analysis of genome-wide association study data., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)