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JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis

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JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis (379.1Kb)
Tarih
2015
Yazar
Kazan, Hilal
Çolak, Recep
Kim, TaeHyung
Oh, Yoomi
Cruz, Miguel
Valladares Salgado, Adan
Peralta, Jesus
Escobedo, Jorge
Parra, Esteban J.
Kim, Philip M.
Goldenberg, Anna
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Özet
Motivation: Rapid advances in genotyping and genome-wide association studies have enabled the discovery of many new genotype–phenotype associations at the resolution of individual markers. However, these associations explain only a small proportion of theoretically estimated heritability of most diseases. In this work, we propose an integrative mixture model called JBASE: joint Bayesian analysis of subphenotypes and epistasis. JBASE explores two major reasons of missing heritability: interactions between genetic variants, a phenomenon known as epistasis and phenotypic heterogeneity, addressed via subphenotyping. Results: Our extensive simulations in a wide range of scenarios repeatedly demonstrate that JBASE can identify true underlying subphenotypes, including their associated variants and their interactions, with high precision. In the presence of phenotypic heterogeneity, JBASE has higher Power and lower Type 1 Error than five state-of-the-art approaches. We applied our method to a sample of individuals from Mexico with Type 2 diabetes and discovered two novel epistatic modules, including two loci each, that define two subphenotypes characterized by differences in body mass index and waist-to-hip ratio. We successfully replicated these subphenotypes and epistatic modules in an independent dataset from Mexico genotyped with a different platform. Availability and implementation: JBASE is implemented in Cþþ, supported on Linux and is available at http://www.cs.toronto.edu/goldenberg/JBASE/jbase.tar.gz. The genotype data underlying this study are available upon approval by the ethics review board of the Medical Centre Siglo XXI.
Bağlantı
http://hdl.handle.net/20.500.12566/179
Koleksiyonlar
  • Bilgisayar Mühendisliği Bölümü / Department of Computer Engineering
  • PubMed İndeksli Yayınlar Koleksiyonu

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