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Full-Text Articles in Life Sciences
Survey Of The Heritability And Sparse Architecture Of Gene Expression Traits Across Human Tissues., Heather E. Wheeler, Kaanan P. Shah, Jonathon Brenner, Tzintzuni Garcia, Keston Aquino-Michaels, Gtex-Consortium, Nancy J. Cox, Dan L. Nicolae, Hae Kyung Im
Survey Of The Heritability And Sparse Architecture Of Gene Expression Traits Across Human Tissues., Heather E. Wheeler, Kaanan P. Shah, Jonathon Brenner, Tzintzuni Garcia, Keston Aquino-Michaels, Gtex-Consortium, Nancy J. Cox, Dan L. Nicolae, Hae Kyung Im
Bioinformatics Faculty Publications
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. Bayesian Sparse Linear Mixed Model (BSLMM) analysis provides strong evidence that the genetic contribution to local expression traits is dominated by …
Pharmacogenetic Discovery In Calgb (Alliance) 90401 And Mechanistic Validation Of A Vac14 Polymorphism That Increases Risk Of Docetaxel-Induced Neuropathy, Daniel L. Hertz, Kouros Owzar, Sherrie Lessans, Claudia Wing, Chen Jiang, William Kevin Kelly, Jai Patel, Susan Halabi, Yoichi Furukawa, Heather E. Wheeler, Alexander B. Sibley, Cameron Lassiter, Lois Weisman, Dorothy Watson, Stefanie D. Krens, Flora Mulkey, Cynthia L. Renn, Eric J. Small, Phillip G. Febbo, Ivo Shterev, Deanna L. Kroetz, Paula N. Friedman, John F. Mahoney, Michael A. Carducci, Michael J. Kelley, Yusuke Nakamura, Michiaki Kubo, Susan G. Dorsey, M. Eileen Dolan, Michael J. Morris, Howard L. Mcleod
Pharmacogenetic Discovery In Calgb (Alliance) 90401 And Mechanistic Validation Of A Vac14 Polymorphism That Increases Risk Of Docetaxel-Induced Neuropathy, Daniel L. Hertz, Kouros Owzar, Sherrie Lessans, Claudia Wing, Chen Jiang, William Kevin Kelly, Jai Patel, Susan Halabi, Yoichi Furukawa, Heather E. Wheeler, Alexander B. Sibley, Cameron Lassiter, Lois Weisman, Dorothy Watson, Stefanie D. Krens, Flora Mulkey, Cynthia L. Renn, Eric J. Small, Phillip G. Febbo, Ivo Shterev, Deanna L. Kroetz, Paula N. Friedman, John F. Mahoney, Michael A. Carducci, Michael J. Kelley, Yusuke Nakamura, Michiaki Kubo, Susan G. Dorsey, M. Eileen Dolan, Michael J. Morris, Howard L. Mcleod
Biology: Faculty Publications and Other Works
Purpose
Discovery of single nucleotide polymorphisms (SNPs) that predict a patient's risk of docetaxel-induced neuropathy would enable treatment individualization to maximize efficacy and avoid unnecessary toxicity. The objectives of this analysis were to discover SNPs associated with docetaxel-induced neuropathy and mechanistically validate these associations in preclinical models of drug-induced neuropathy.
Experimental Design
A genome-wide association study was conducted in metastatic castrate-resistant prostate cancer patients treated with docetaxel, prednisone and randomized to bevacizumab or placebo on CALGB 90401. SNPs were genotyped on the Illumina HumanHap610-Quad platform followed by rigorous quality control. The inference was conducted on the cumulative dose at occurrence …