Literature DB >> 28893853

A Powerful Framework for Integrating eQTL and GWAS Summary Data.

Zhiyuan Xu1, Chong Wu1, Peng Wei2, Wei Pan3.   

Abstract

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. The proposed test was applied to several GWAS datasets, including two lipid summary association datasets based on [Formula: see text] and [Formula: see text] samples, respectively, and uncovered more known or novel trait-associated genes, showcasing much improved performance of our proposed method. The software implementing the proposed method is freely available as an R package.
Copyright © 2017 by the Genetics Society of America.

Entities:  

Keywords:  Sum test; aSPU test; statistical power; transcriptome-wide association study (TWAS); weighted association testing

Mesh:

Year:  2017        PMID: 28893853      PMCID: PMC5676241          DOI: 10.1534/genetics.117.300270

Source DB:  PubMed          Journal:  Genetics        ISSN: 0016-6731            Impact factor:   4.562


  36 in total

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Review 2.  Genomic similarity and kernel methods I: advancements by building on mathematical and statistical foundations.

Authors:  Daniel J Schaid
Journal:  Hum Hered       Date:  2010-07-03       Impact factor: 0.444

3.  Using linkage genome scans to improve power of association in genome scans.

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4.  Generalized genomic distance-based regression methodology for multilocus association analysis.

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Journal:  Am J Hum Genet       Date:  2006-09-21       Impact factor: 11.025

5.  A map of human genome variation from population-scale sequencing.

Authors:  Gonçalo R Abecasis; David Altshuler; Adam Auton; Lisa D Brooks; Richard M Durbin; Richard A Gibbs; Matt E Hurles; Gil A McVean
Journal:  Nature       Date:  2010-10-28       Impact factor: 49.962

6.  Asymptotic tests of association with multiple SNPs in linkage disequilibrium.

Authors:  Wei Pan
Journal:  Genet Epidemiol       Date:  2009-09       Impact factor: 2.135

7.  Trait-associated SNPs are more likely to be eQTLs: annotation to enhance discovery from GWAS.

Authors:  Dan L Nicolae; Eric Gamazon; Wei Zhang; Shiwei Duan; M Eileen Dolan; Nancy J Cox
Journal:  PLoS Genet       Date:  2010-04-01       Impact factor: 5.917

8.  Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.

Authors:  Andre Franke; Dermot P B McGovern; Jeffrey C Barrett; Kai Wang; Graham L Radford-Smith; Tariq Ahmad; Charlie W Lees; Tobias Balschun; James Lee; Rebecca Roberts; Carl A Anderson; Joshua C Bis; Suzanne Bumpstead; David Ellinghaus; Eleonora M Festen; Michel Georges; Todd Green; Talin Haritunians; Luke Jostins; Anna Latiano; Christopher G Mathew; Grant W Montgomery; Natalie J Prescott; Soumya Raychaudhuri; Jerome I Rotter; Philip Schumm; Yashoda Sharma; Lisa A Simms; Kent D Taylor; David Whiteman; Cisca Wijmenga; Robert N Baldassano; Murray Barclay; Theodore M Bayless; Stephan Brand; Carsten Büning; Albert Cohen; Jean-Frederick Colombel; Mario Cottone; Laura Stronati; Ted Denson; Martine De Vos; Renata D'Inca; Marla Dubinsky; Cathryn Edwards; Tim Florin; Denis Franchimont; Richard Gearry; Jürgen Glas; Andre Van Gossum; Stephen L Guthery; Jonas Halfvarson; Hein W Verspaget; Jean-Pierre Hugot; Amir Karban; Debby Laukens; Ian Lawrance; Marc Lemann; Arie Levine; Cecile Libioulle; Edouard Louis; Craig Mowat; William Newman; Julián Panés; Anne Phillips; Deborah D Proctor; Miguel Regueiro; Richard Russell; Paul Rutgeerts; Jeremy Sanderson; Miquel Sans; Frank Seibold; A Hillary Steinhart; Pieter C F Stokkers; Leif Torkvist; Gerd Kullak-Ublick; David Wilson; Thomas Walters; Stephan R Targan; Steven R Brant; John D Rioux; Mauro D'Amato; Rinse K Weersma; Subra Kugathasan; Anne M Griffiths; John C Mansfield; Severine Vermeire; Richard H Duerr; Mark S Silverberg; Jack Satsangi; Stefan Schreiber; Judy H Cho; Vito Annese; Hakon Hakonarson; Mark J Daly; Miles Parkes
Journal:  Nat Genet       Date:  2010-12       Impact factor: 38.330

9.  Biological, clinical and population relevance of 95 loci for blood lipids.

Authors:  Tanya M Teslovich; Kiran Musunuru; Albert V Smith; Andrew C Edmondson; Ioannis M Stylianou; Masahiro Koseki; James P Pirruccello; Samuli Ripatti; Daniel I Chasman; Cristen J Willer; Christopher T Johansen; Sigrid W Fouchier; Aaron Isaacs; Gina M Peloso; Maja Barbalic; Sally L Ricketts; Joshua C Bis; Yurii S Aulchenko; Gudmar Thorleifsson; Mary F Feitosa; John Chambers; Marju Orho-Melander; Olle Melander; Toby Johnson; Xiaohui Li; Xiuqing Guo; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C Croteau-Chonka; Leslie A Lange; Joshua D Smith; Kijoung Song; Jing Hua Zhao; Xin Yuan; Jian'an Luan; Claudia Lamina; Andreas Ziegler; Weihua Zhang; Robert Y L Zee; Alan F Wright; Jacqueline C M Witteman; James F Wilson; Gonneke Willemsen; H-Erich Wichmann; John B Whitfield; Dawn M Waterworth; Nicholas J Wareham; Gérard Waeber; Peter Vollenweider; Benjamin F Voight; Veronique Vitart; Andre G Uitterlinden; Manuela Uda; Jaakko Tuomilehto; John R Thompson; Toshiko Tanaka; Ida Surakka; Heather M Stringham; Tim D Spector; Nicole Soranzo; Johannes H Smit; Juha Sinisalo; Kaisa Silander; Eric J G Sijbrands; Angelo Scuteri; James Scott; David Schlessinger; Serena Sanna; Veikko Salomaa; Juha Saharinen; Chiara Sabatti; Aimo Ruokonen; Igor Rudan; Lynda M Rose; Robert Roberts; Mark Rieder; Bruce M Psaty; Peter P Pramstaller; Irene Pichler; Markus Perola; Brenda W J H Penninx; Nancy L Pedersen; Cristian Pattaro; Alex N Parker; Guillaume Pare; Ben A Oostra; Christopher J O'Donnell; Markku S Nieminen; Deborah A Nickerson; Grant W Montgomery; Thomas Meitinger; Ruth McPherson; Mark I McCarthy; Wendy McArdle; David Masson; Nicholas G Martin; Fabio Marroni; Massimo Mangino; Patrik K E Magnusson; Gavin Lucas; Robert Luben; Ruth J F Loos; Marja-Liisa Lokki; Guillaume Lettre; Claudia Langenberg; Lenore J Launer; Edward G Lakatta; Reijo Laaksonen; Kirsten O Kyvik; Florian Kronenberg; Inke R König; Kay-Tee Khaw; Jaakko Kaprio; Lee M Kaplan; Asa Johansson; Marjo-Riitta Jarvelin; A Cecile J W Janssens; Erik Ingelsson; Wilmar Igl; G Kees Hovingh; Jouke-Jan Hottenga; Albert Hofman; Andrew A Hicks; Christian Hengstenberg; Iris M Heid; Caroline Hayward; Aki S Havulinna; Nicholas D Hastie; Tamara B Harris; Talin Haritunians; Alistair S Hall; Ulf Gyllensten; Candace Guiducci; Leif C Groop; Elena Gonzalez; Christian Gieger; Nelson B Freimer; Luigi Ferrucci; Jeanette Erdmann; Paul Elliott; Kenechi G Ejebe; Angela Döring; Anna F Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Eco J C de Geus; Ulf de Faire; Gabriel Crawford; Francis S Collins; Yii-der I Chen; Mark J Caulfield; Harry Campbell; Noel P Burtt; Lori L Bonnycastle; Dorret I Boomsma; S Matthijs Boekholdt; Richard N Bergman; Inês Barroso; Stefania Bandinelli; Christie M Ballantyne; Themistocles L Assimes; Thomas Quertermous; David Altshuler; Mark Seielstad; Tien Y Wong; E-Shyong Tai; Alan B Feranil; Christopher W Kuzawa; Linda S Adair; Herman A Taylor; Ingrid B Borecki; Stacey B Gabriel; James G Wilson; Hilma Holm; Unnur Thorsteinsdottir; Vilmundur Gudnason; Ronald M Krauss; Karen L Mohlke; Jose M Ordovas; Patricia B Munroe; Jaspal S Kooner; Alan R Tall; Robert A Hegele; John J P Kastelein; Eric E Schadt; Jerome I Rotter; Eric Boerwinkle; David P Strachan; Vincent Mooser; Kari Stefansson; Muredach P Reilly; Nilesh J Samani; Heribert Schunkert; L Adrienne Cupples; Manjinder S Sandhu; Paul M Ridker; Daniel J Rader; Cornelia M van Duijn; Leena Peltonen; Gonçalo R Abecasis; Michael Boehnke; Sekar Kathiresan
Journal:  Nature       Date:  2010-08-05       Impact factor: 49.962

10.  Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

Authors: 
Journal:  Nature       Date:  2007-06-07       Impact factor: 49.962

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  33 in total

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2.  A powerful fine-mapping method for transcriptome-wide association studies.

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3.  Improved Use of Small Reference Panels for Conditional and Joint Analysis with GWAS Summary Statistics.

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Journal:  Genetics       Date:  2018-04-19       Impact factor: 4.562

4.  Integration of methylation QTL and enhancer-target gene maps with schizophrenia GWAS summary results identifies novel genes.

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Journal:  Bioinformatics       Date:  2019-10-01       Impact factor: 6.937

5.  Integration of Enhancer-Promoter Interactions with GWAS Summary Results Identifies Novel Schizophrenia-Associated Genes and Pathways.

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Journal:  Genetics       Date:  2018-05-04       Impact factor: 4.562

6.  Leveraging existing GWAS summary data of genetically correlated and uncorrelated traits to improve power for a new GWAS.

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Journal:  Genet Epidemiol       Date:  2020-07-16       Impact factor: 2.135

7.  Integrating eQTL data with GWAS summary statistics in pathway-based analysis with application to schizophrenia.

Authors:  Chong Wu; Wei Pan
Journal:  Genet Epidemiol       Date:  2018-02-07       Impact factor: 2.135

8.  Incorporating multiple sets of eQTL weights into gene-by-environment interaction analysis identifies novel susceptibility loci for pancreatic cancer.

Authors:  Tianzhong Yang; Hongwei Tang; Harvey A Risch; Sarah H Olson; Gloria Peterson; Paige M Bracci; Steven Gallinger; Rayjean J Hung; Rachel E Neale; Ghislaine Scelo; Eric J Duell; Robert C Kurtz; Kay-Tee Khaw; Gianluca Severi; Malin Sund; Nick Wareham; Christopher I Amos; Donghui Li; Peng Wei
Journal:  Genet Epidemiol       Date:  2020-08-10       Impact factor: 2.135

9.  Some statistical consideration in transcriptome-wide association studies.

Authors:  Haoran Xue; Wei Pan
Journal:  Genet Epidemiol       Date:  2019-12-10       Impact factor: 2.135

10.  Integrating germline and somatic genetics to identify genes associated with lung cancer.

Authors:  Jack Pattee; Xiaowei Zhan; Guanghua Xiao; Wei Pan
Journal:  Genet Epidemiol       Date:  2019-12-10       Impact factor: 2.135

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