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PrediXcan

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https://www.readbyqxmd.com/read/29752479/publisher-correction-genome-wide-association-study-of-delay-discounting-in-23-217-adult-research-participants-of-european-ancestry
#1
Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L Elson, Anita Pandit, Ellen M Schmidt, Johanna R Foerster, Gonçalo R Abecasis, Joshua C Gray, Harriet de Wit, Lea K Davis, James MacKillop, Abraham A Palmer
In the version of this article initially published, the consortium authorship was not presented correctly. The 23andMe Research Team was listed as the last author, rather than the fourth, and a line directing readers to the Supplementary Note for a list of members did appear but was not directly associated with the consortium name. Also, the Supplementary Note description stated that both member names and affiliations were included; in fact, only names are given. Finally, the URL for S-PrediXcan was given in the Methods as https://github...
May 11, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29739930/exploring-the-phenotypic-consequences-of-tissue-specific-gene-expression-variation-inferred-from-gwas-summary-statistics
#2
Alvaro N Barbeira, Scott P Dickinson, Rodrigo Bonazzola, Jiamao Zheng, Heather E Wheeler, Jason M Torres, Eric S Torstenson, Kaanan P Shah, Tzintzuni Garcia, Todd L Edwards, Eli A Stahl, Laura M Huckins, Dan L Nicolae, Nancy J Cox, Hae Kyung Im
Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes...
May 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29727690/a-mixed-effects-model-for-powerful-association-tests-in-integrative-functional-genomics
#3
Yu-Ru Su, Chongzhi Di, Stephanie Bien, Licai Huang, Xinyuan Dong, Goncalo Abecasis, Sonja Berndt, Stephane Bezieau, Hermann Brenner, Bette Caan, Graham Casey, Jenny Chang-Claude, Stephen Chanock, Sai Chen, Charles Connolly, Keith Curtis, Jane Figueiredo, Manish Gala, Steven Gallinger, Tabitha Harrison, Michael Hoffmeister, John Hopper, Jeroen R Huyghe, Mark Jenkins, Amit Joshi, Loic Le Marchand, Polly Newcomb, Deborah Nickerson, John Potter, Robert Schoen, Martha Slattery, Emily White, Brent Zanke, Ulrike Peters, Li Hsu
Genome-wide association studies (GWASs) have successfully identified thousands of genetic variants for many complex diseases; however, these variants explain only a small fraction of the heritability. Recently, genetic association studies that leverage external transcriptome data have received much attention and shown promise for discovering novel variants. One such approach, PrediXcan, is to use predicted gene expression through genetic regulation. However, there are limitations in this approach. The predicted gene expression may be biased, resulting from regularized regression applied to moderately sample-sized reference studies...
May 3, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29404214/gene-based-association-study-for-lipid-traits-in-diverse-cohorts-implicates-bace1-and-sidt2-regulation-in-triglyceride-levels
#4
Angela Andaleon, Lauren S Mogil, Heather E Wheeler
Plasma lipid levels are risk factors for cardiovascular disease, a leading cause of death worldwide. While many studies have been conducted on lipid genetics, they mainly focus on Europeans and thus their transferability to diverse populations is unclear. We performed SNP- and gene-level genome-wide association studies (GWAS) of four lipid traits in cohorts from Nigeria and the Philippines and compared them to the results of larger, predominantly European meta-analyses. Two previously implicated loci met genome-wide significance in our SNP-level GWAS in the Nigerian cohort, rs34065661 in CETP associated with HDL cholesterol ( P  = 9...
2018: PeerJ
https://www.readbyqxmd.com/read/29218904/evaluation-of-predixcan-for-prioritizing-gwas-associations-and-predicting-gene-expression
#5
Binglan Li, Shefali S Verma, Yogasudha C Veturi, Anurag Verma, Yuki Bradford, David W Haas, Marylyn D Ritchie
Genome-wide association studies (GWAS) have been successful in facilitating the understanding of genetic architecture behind human diseases, but this approach faces many challenges. To identify disease-related loci with modest to weak effect size, GWAS requires very large sample sizes, which can be computational burdensome. In addition, the interpretation of discovered associations remains difficult. PrediXcan was developed to help address these issues. With built in SNP-expression models, PrediXcan is able to predict the expression of genes that are regulated by putative expression quantitative trait loci (eQTLs), and these predicted expression levels can then be used to perform gene-based association studies...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29127305/cis-snps-set-testing-and-predixcan-analysis-for-gene-expression-data-using-linear-mixed-models
#6
Ping Zeng, Ting Wang, Shuiping Huang
Understanding the functional mechanism of SNPs identified in GWAS on complex diseases is currently a challenging task. The studies of expression quantitative trait loci (eQTL) have shown that regulatory variants play a crucial role in the function of associated SNPs. Detecting significant genes (called eGenes) in eQTL studies and analyzing the effect sizes of cis-SNPs can offer important implications on the genetic architecture of associated SNPs and interpretations of the molecular basis of diseases. We applied linear mixed models (LMM) to the gene expression level and constructed likelihood ratio tests (LRT) to test for eGene in the Geuvadis data...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28893853/a-powerful-framework-for-integrating-eqtl-and-gwas-summary-data
#7
Zhiyuan Xu, Chong Wu, Peng Wei, Wei Pan
Two new gene-based association analysis methods, called PrediXcan and TWAS for GWAS individual-level and summary data, respectively, were recently proposed to integrate GWAS with eQTL data, alleviating two common problems in GWAS by boosting statistical power and facilitating biological interpretation of GWAS discoveries. Based on a novel reformulation of PrediXcan and TWAS, we propose a more powerful gene-based association test to integrate single set or multiple sets of eQTL data with GWAS individual-level data or summary statistics...
November 2017: Genetics
https://www.readbyqxmd.com/read/28878256/non-parametric-genetic-prediction-of-complex-traits-with-latent-dirichlet-process-regression-models
#8
Ping Zeng, Xiang Zhou
Using genotype data to perform accurate genetic prediction of complex traits can facilitate genomic selection in animal and plant breeding programs, and can aid in the development of personalized medicine in humans. Because most complex traits have a polygenic architecture, accurate genetic prediction often requires modeling all genetic variants together via polygenic methods. Here, we develop such a polygenic method, which we refer to as the latent Dirichlet process regression model. Dirichlet process regression is non-parametric in nature, relies on the Dirichlet process to flexibly and adaptively model the effect size distribution, and thus enjoys robust prediction performance across a broad spectrum of genetic architectures...
September 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28611204/clinical-and-genome-wide-analysis-of-cisplatin-induced-peripheral-neuropathy-in-survivors-of-adult-onset-cancer
#9
M Eileen Dolan, Omar El Charif, Heather E Wheeler, Eric R Gamazon, Shirin Ardeshir-Rouhani-Fard, Patrick Monahan, Darren R Feldman, Robert J Hamilton, David J Vaughn, Clair J Beard, Chunkit Fung, Jeri Kim, Sophie D Fossa, Daniel L Hertz, Taisei Mushiroda, Michiaki Kubo, Lawrence H Einhorn, Nancy J Cox, Lois B Travis
Purpose: Our purpose was to characterize the clinical influences, genetic risk factors, and gene mechanisms contributing to persistent cisplatin-induced peripheral neuropathy (CisIPN) in testicular cancer survivors (TCSs).Experimental Design: TCS given cisplatin-based therapy completed the validated EORTC QLQ-CIPN20 questionnaire. An ordinal CisIPN phenotype was derived, and associations with age, smoking, excess drinking, hypertension, body mass index, diabetes, hypercholesterolemia, cumulative cisplatin dose, and self-reported health were examined for 680 TCS...
October 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27835642/survey-of-the-heritability-and-sparse-architecture-of-gene-expression-traits-across-human-tissues
#10
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
#11
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...
April 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/26258848/a-gene-based-association-method-for-mapping-traits-using-reference-transcriptome-data
#12
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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