We consider likelihood ratio tests (LRT) and their modifications for homogeneity in admixture models. The admixture model is a two-component mixture model, where one component is indexed by an unknown parameter while the parameter value for the other component is known. This model is widely used in genetic linkage analysis under heterogeneity in which the kernel distribution is binomial. For such models, it is long recognized that testing for homogeneity is nonstandard, and the LRT statistic does not converge to a conventional χ(2) distribution. In this article, we investigate the asymptotic behavior of the LRT for general admixture models and show that its limiting distribution is equivalent to the supremum of a squared Gaussian process. We also discuss the connection and comparison between LRT and alternative approaches such as modifications of LRT and score tests, including the modified LRT (Fu, Chen, and Kalbfleisch, 2006, Statistica Sinica 16, 805-823). The LRT is an omnibus test that is powerful to detect general alternative hypotheses. In contrast, alternative approaches may be slightly more powerful to detect certain type of alternatives, but much less powerful for others. Our results are illustrated by simulation studies and an application to a genetic linkage study of schizophrenia.
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http://dx.doi.org/10.1111/j.1541-0420.2011.01574.x | DOI Listing |
Sci Rep
January 2025
Department of Radiation Oncology, Henry Ford Hospital, Detroit, USA.
Best current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel's CA time-trace.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Dipartimento di Scienze Linguistiche e Letterature Straniere, Università Cattolica del Sacro Cuore, Largo Gemelli 1, 20123 Milan, Italy.
Eastern Finnic populations, including Karelians, Veps, Votes, Ingrians, and Ingrian Finns, are a significant component of the history of Finnic populations, which have developed over ~3 kya. Yet, these groups remain understudied from a genetic point of view. In this work, we explore the gene pools of Karelians (Northern, Tver, Ludic, and Livvi), Veps, Ingrians, Votes, and Ingrian Finns using Y-chromosome markers (N = 357) and genome-wide autosomes (N = 67) and in comparison with selected Russians populations of the area (N = 763).
View Article and Find Full Text PDFbioRxiv
December 2024
Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ 08544, USA.
The admixture model is widely applied to estimate and interpret population structure among individuals. Here we consider a "standard admixture" model that assumes the admixed populations are unrelated and also a generalized model, where the admixed populations themselves are related via coancestry (or covariance) of allele frequencies. The generalized model yields a potentially more realistic and substantially more flexible model that we call "super admixture".
View Article and Find Full Text PDFmedRxiv
December 2024
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.
View Article and Find Full Text PDFAm J Hum Genet
December 2024
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; The Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA. Electronic address:
In recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using local ancestry inference (LAI). Accurate LAI is crucial to ensure that downstream analyses accurately reflect the genetic ancestry of research participants. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America's primary continental ancestries-African (AFR), Amerindigenous (AMR), and European (EUR).
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