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PrediXcan

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https://www.readbyqxmd.com/read/27835642/survey-of-the-heritability-and-sparse-architecture-of-gene-expression-traits-across-human-tissues
#1
Heather E Wheeler, Kaanan P Shah, Jonathon Brenner, Tzintzuni Garcia, Keston Aquino-Michaels, Nancy J Cox, Dan L Nicolae, Hae Kyung Im
Understanding the genetic architecture of gene expression traits is key to elucidating the underlying mechanisms of complex traits. Here, for the first time, we perform a systematic survey of the heritability and the distribution of effect sizes across all representative tissues in the human body. We find that local h2 can be relatively well characterized with 59% of expressed genes showing significant h2 (FDR < 0.1) in the DGN whole blood cohort. However, current sample sizes (n ≤ 922) do not allow us to compute distal h2...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27743375/genetic-resilience-to-amyloid-related-cognitive-decline
#2
Timothy J Hohman, Logan Dumitrescu, Nancy J Cox, Angela L Jefferson
Preclinical Alzheimer's disease (AD) is characterized by amyloid deposition in the absence of overt clinical impairment. There is substantial heterogeneity in the long-term clinical outcomes among amyloid positive individuals, yet limited work has focused on identifying molecular factors driving resilience from amyloid-related cognitive impairment. We apply a recently developed predicted gene expression analysis (PrediXcan) to identify genes that modify the association between baseline amyloid deposition and longitudinal cognitive changes...
October 14, 2016: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/26258848/a-gene-based-association-method-for-mapping-traits-using-reference-transcriptome-data
#3
Eric R Gamazon, Heather E Wheeler, Kaanan P Shah, Sahar V Mozaffari, Keston Aquino-Michaels, Robert J Carroll, Anne E Eyler, Joshua C Denny, Dan L Nicolae, Nancy J Cox, Hae Kyung Im
Genome-wide association studies (GWAS) have identified thousands of variants robustly associated with complex traits. However, the biological mechanisms underlying these associations are, in general, not well understood. We propose a gene-based association method called PrediXcan that directly tests the molecular mechanisms through which genetic variation affects phenotype. The approach estimates the component of gene expression determined by an individual's genetic profile and correlates 'imputed' gene expression with the phenotype under investigation to identify genes involved in the etiology of the phenotype...
September 2015: Nature Genetics
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