Literature DB >> 24013639

Systematic identification of trans eQTLs as putative drivers of known disease associations.

Harm-Jan Westra1, Marjolein J Peters2,3, Tõnu Esko4, Hanieh Yaghootkar5, Claudia Schurmann6, Johannes Kettunen7,8, Mark W Christiansen9, Bruce M Psaty9,10, Samuli Ripatti7,8,11, Alexander Teumer6, Timothy M Frayling5, Andres Metspalu4, Joyce B J van Meurs2,3, Lude Franke1, Benjamin P Fairfax12,13, Katharina Schramm14,15, Joseph E Powell16,17, Alexandra Zhernakova1, Daria V Zhernakova1, Jan H Veldink18, Leonard H Van den Berg18, Juha Karjalainen1, Sebo Withoff1, André G Uitterlinden2,3,19, Albert Hofman3,19, Fernando Rivadeneira2,3,19, Peter A C 't Hoen20, Eva Reinmaa4, Krista Fischer4, Mari Nelis4, Lili Milani4, David Melzer21, Luigi Ferrucci22, Andrew B Singleton23, Dena G Hernandez23,24, Michael A Nalls23, Georg Homuth6, Matthias Nauck25, Dörte Radke26, Uwe Völker6, Markus Perola4,8, Veikko Salomaa8, Jennifer Brody9, Astrid Suchy-Dicey27, Sina A Gharib28, Daniel A Enquobahrie27, Thomas Lumley29, Grant W Montgomery30, Seiko Makino12, Holger Prokisch14,15, Christian Herder31, Michael Roden31,32, Harald Grallert33, Thomas Meitinger14,15,34, Konstantin Strauch35,36, Yang Li37, Ritsert C Jansen37, Peter M Visscher16,17, Julian C Knight12.   

Abstract

Identifying the downstream effects of disease-associated SNPs is challenging. To help overcome this problem, we performed expression quantitative trait locus (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311 individuals with replication in 2,775 individuals. We identified and replicated trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously associated with complex traits at genome-wide significance. Some of these SNPs affect multiple genes in trans that are known to be altered in individuals with disease: rs4917014, previously associated with systemic lupus erythematosus (SLE), altered gene expression of C1QB and five type I interferon response genes, both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly alters the 3' UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal gene. Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.

Entities:  

Mesh：

Year:  2013        PMID： 24013639      PMCID： PMC3991562          DOI： 10.1038/ng.2756

Source DB:  PubMed          Journal:  Nat Genet        ISSN： 1061-4036            Impact factor:   38.330


  57 in total

1.  Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.

Authors:  Lucia A Hindorff; Praveen Sethupathy; Heather A Junkins; Erin M Ramos; Jayashri P Mehta; Francis S Collins; Teri A Manolio
Journal:  Proc Natl Acad Sci U S A       Date:  2009-05-27       Impact factor: 11.205

2.  Activation of type I interferon system in systemic lupus erythematosus correlates with disease activity but not with antiretroviral antibodies.

Authors:  A A Bengtsson; G Sturfelt; L Truedsson; J Blomberg; G Alm; H Vallin; L Rönnblom
Journal:  Lupus       Date:  2000       Impact factor: 2.911

3.  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

4.  The risk of myocardial infarction associated with antihypertensive drug therapies.

Authors:  B M Psaty; S R Heckbert; T D Koepsell; D S Siscovick; T E Raghunathan; N S Weiss; F R Rosendaal; R N Lemaitre; N L Smith; P W Wahl
Journal:  JAMA       Date:  1995 Aug 23-30       Impact factor: 56.272

5.  Understanding mechanisms underlying human gene expression variation with RNA sequencing.

Authors:  Joseph K Pickrell; John C Marioni; Athma A Pai; Jacob F Degner; Barbara E Engelhardt; Everlyne Nkadori; Jean-Baptiste Veyrieras; Matthew Stephens; Yoav Gilad; Jonathan K Pritchard
Journal:  Nature       Date:  2010-03-10       Impact factor: 49.962

6.  Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Authors:  Louise V Wain; Germaine C Verwoert; Paul F O'Reilly; Gang Shi; Toby Johnson; Andrew D Johnson; Murielle Bochud; Kenneth M Rice; Peter Henneman; Albert V Smith; Georg B Ehret; Najaf Amin; Martin G Larson; Vincent Mooser; David Hadley; Marcus Dörr; Joshua C Bis; Thor Aspelund; Tõnu Esko; A Cecile J W Janssens; Jing Hua Zhao; Simon Heath; Maris Laan; Jingyuan Fu; Giorgio Pistis; Jian'an Luan; Pankaj Arora; Gavin Lucas; Nicola Pirastu; Irene Pichler; Anne U Jackson; Rebecca J Webster; Feng Zhang; John F Peden; Helena Schmidt; Toshiko Tanaka; Harry Campbell; Wilmar Igl; Yuri Milaneschi; Jouke-Jan Hottenga; Veronique Vitart; Daniel I Chasman; Stella Trompet; Jennifer L Bragg-Gresham; Behrooz Z Alizadeh; John C Chambers; Xiuqing Guo; Terho Lehtimäki; Brigitte Kühnel; Lorna M Lopez; Ozren Polašek; Mladen Boban; Christopher P Nelson; Alanna C Morrison; Vasyl Pihur; Santhi K Ganesh; Albert Hofman; Suman Kundu; Francesco U S Mattace-Raso; Fernando Rivadeneira; Eric J G Sijbrands; Andre G Uitterlinden; Shih-Jen Hwang; Ramachandran S Vasan; Thomas J Wang; Sven Bergmann; Peter Vollenweider; Gérard Waeber; Jaana Laitinen; Anneli Pouta; Paavo Zitting; Wendy L McArdle; Heyo K Kroemer; Uwe Völker; Henry Völzke; Nicole L Glazer; Kent D Taylor; Tamara B Harris; Helene Alavere; Toomas Haller; Aime Keis; Mari-Liis Tammesoo; Yurii Aulchenko; Inês Barroso; Kay-Tee Khaw; Pilar Galan; Serge Hercberg; Mark Lathrop; Susana Eyheramendy; Elin Org; Siim Sõber; Xiaowen Lu; Ilja M Nolte; Brenda W Penninx; Tanguy Corre; Corrado Masciullo; Cinzia Sala; Leif Groop; Benjamin F Voight; Olle Melander; Christopher J O'Donnell; Veikko Salomaa; Adamo Pio d'Adamo; Antonella Fabretto; Flavio Faletra; Sheila Ulivi; Fabiola M Del Greco; Maurizio Facheris; Francis S Collins; Richard N Bergman; John P Beilby; Joseph Hung; A William Musk; Massimo Mangino; So-Youn Shin; Nicole Soranzo; Hugh Watkins; Anuj Goel; Anders Hamsten; Pierre Gider; Marisa Loitfelder; Marion Zeginigg; Dena Hernandez; Samer S Najjar; Pau Navarro; Sarah H Wild; Anna Maria Corsi; Andrew Singleton; Eco J C de Geus; Gonneke Willemsen; Alex N Parker; Lynda M Rose; Brendan Buckley; David Stott; Marco Orru; Manuela Uda; Melanie M van der Klauw; Weihua Zhang; Xinzhong Li; James Scott; Yii-Der Ida Chen; Gregory L Burke; Mika Kähönen; Jorma Viikari; Angela Döring; Thomas Meitinger; Gail Davies; John M Starr; Valur Emilsson; Andrew Plump; Jan H Lindeman; Peter A C 't Hoen; Inke R König; Janine F Felix; Robert Clarke; Jemma C Hopewell; Halit Ongen; Monique Breteler; Stéphanie Debette; Anita L Destefano; Myriam Fornage; Gary F Mitchell; Nicholas L Smith; Hilma Holm; Kari Stefansson; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Nilesh J Samani; Michael Preuss; Igor Rudan; Caroline Hayward; Ian J Deary; H-Erich Wichmann; Olli T Raitakari; Walter Palmas; Jaspal S Kooner; Ronald P Stolk; J Wouter Jukema; Alan F Wright; Dorret I Boomsma; Stefania Bandinelli; Ulf B Gyllensten; James F Wilson; Luigi Ferrucci; Reinhold Schmidt; Martin Farrall; Tim D Spector; Lyle J Palmer; Jaakko Tuomilehto; Arne Pfeufer; Paolo Gasparini; David Siscovick; David Altshuler; Ruth J F Loos; Daniela Toniolo; Harold Snieder; Christian Gieger; Pierre Meneton; Nicholas J Wareham; Ben A Oostra; Andres Metspalu; Lenore Launer; Rainer Rettig; David P Strachan; Jacques S Beckmann; Jacqueline C M Witteman; Jeanette Erdmann; Ko Willems van Dijk; Eric Boerwinkle; Michael Boehnke; Paul M Ridker; Marjo-Riitta Jarvelin; Aravinda Chakravarti; Goncalo R Abecasis; Vilmundur Gudnason; Christopher Newton-Cheh; Daniel Levy; Patricia B Munroe; Bruce M Psaty; Mark J Caulfield; Dabeeru C Rao; Martin D Tobin; Paul Elliott; Cornelia M van Duijn
Journal:  Nat Genet       Date:  2011-09-11       Impact factor: 38.330

7.  A genome-wide association study of the metabolic syndrome in Indian Asian men.

Authors:  Delilah Zabaneh; David J Balding
Journal:  PLoS One       Date:  2010-08-04       Impact factor: 3.240

8.  The Rotterdam Study: 2012 objectives and design update.

Authors:  Albert Hofman; Cornelia M van Duijn; Oscar H Franco; M Arfan Ikram; Harry L A Janssen; Caroline C W Klaver; Ernst J Kuipers; Tamar E C Nijsten; Bruno H Ch Stricker; Henning Tiemeier; André G Uitterlinden; Meike W Vernooij; Jacqueline C M Witteman
Journal:  Eur J Epidemiol       Date:  2011-08-30       Impact factor: 8.082

9.  Novel associations for hypothyroidism include known autoimmune risk loci.

Authors:  Nicholas Eriksson; Joyce Y Tung; Amy K Kiefer; David A Hinds; Uta Francke; Joanna L Mountain; Chuong B Do
Journal:  PLoS One       Date:  2012-04-06       Impact factor: 3.240

10.  Interferon and granulopoiesis signatures in systemic lupus erythematosus blood.

Authors:  Lynda Bennett; A Karolina Palucka; Edsel Arce; Victoria Cantrell; Josef Borvak; Jacques Banchereau; Virginia Pascual
Journal:  J Exp Med       Date:  2003-03-17       Impact factor: 14.307
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  871 in total

1.  Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis.

Authors:  Javier Gutierrez-Achury; Maria Magdalena Zorro; Isis Ricaño-Ponce; Daria V Zhernakova; Dorothée Diogo; Soumya Raychaudhuri; Lude Franke; Gosia Trynka; Cisca Wijmenga; Alexandra Zhernakova
Journal:  Hum Mol Genet       Date:  2015-11-05       Impact factor: 6.150

2.  Hypoxia-Sensitive COMMD1 Integrates Signaling and Cellular Metabolism in Human Macrophages and Suppresses Osteoclastogenesis.

Authors:  Koichi Murata; Celestia Fang; Chikashi Terao; Eugenia G Giannopoulou; Ye Ji Lee; Min Joon Lee; Se-Hwan Mun; Seyeon Bae; Yu Qiao; Ruoxi Yuan; Moritoshi Furu; Hiromu Ito; Koichiro Ohmura; Shuichi Matsuda; Tsuneyo Mimori; Fumihiko Matsuda; Kyung-Hyun Park-Min; Lionel B Ivashkiv
Journal:  Immunity       Date:  2017-07-18       Impact factor: 31.745

Review 3.  Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases.

Authors:  Gosia Trynka; Soumya Raychaudhuri
Journal:  Curr Opin Genet Dev       Date:  2013-11-25       Impact factor: 5.578

4.  An APOE-independent cis-eSNP on chromosome 19q13.32 influences tau levels and late-onset Alzheimer's disease risk.

Authors:  Shuquan Rao; Mahdi Ghani; Zhiyun Guo; Yuetiva Deming; Kesheng Wang; Rebecca Sims; Canquan Mao; Yao Yao; Carlos Cruchaga; Dietrich A Stephan; Ekaterina Rogaeva
Journal:  Neurobiol Aging       Date:  2018-01-03       Impact factor: 4.673

5.  Trans Effects on Gene Expression Can Drive Omnigenic Inheritance.

Authors:  Xuanyao Liu; Yang I Li; Jonathan K Pritchard
Journal:  Cell       Date:  2019-05-02       Impact factor: 41.582

Review 6.  Determining causality and consequence of expression quantitative trait loci.

Authors:  A Battle; S B Montgomery
Journal:  Hum Genet       Date:  2014-04-26       Impact factor: 4.132

7.  Association of a single nucleotide polymorphism in TNIP1 with type-1 autoimmune hepatitis in the Japanese population.

Authors:  Shomi Oka; Takashi Higuchi; Hiroshi Furukawa; Minoru Nakamura; Atsumasa Komori; Seigo Abiru; Shinya Nagaoka; Satoru Hashimoto; Atsushi Naganuma; Noriaki Naeshiro; Kaname Yoshizawa; Masaaki Shimada; Hideo Nishimura; Minoru Tomizawa; Masahiro Kikuchi; Fujio Makita; Haruhiro Yamashita; Keisuke Ario; Hiroshi Yatsuhashi; Shigeto Tohma; Aya Kawasaki; Naoyuki Tsuchiya; Kiyoshi Migita
Journal:  J Hum Genet       Date:  2018-03-20       Impact factor: 3.172

8.  Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer.

Authors:  Kathryn J Ruddy; Daniel J Schaid; Ann H Partridge; Nicholas B Larson; Anthony Batzler; Lothar Häberle; Ralf Dittrich; Peter Widschwendter; Visnja Fink; Emanuel Bauer; Judith Schwitulla; Matthias Rübner; Arif B Ekici; Viktoria Aivazova-Fuchs; Elizabeth A Stewart; Matthias W Beckmann; Elizabeth Ginsburg; Liewei Wang; Richard M Weinshilboum; Fergus J Couch; Wolfgang Janni; Brigitte Rack; Celine Vachon; Peter A Fasching
Journal:  Fertil Steril       Date:  2019-07-29       Impact factor: 7.329

9.  Characterization of candidate genes in inflammatory bowel disease-associated risk loci.

Authors:  Joanna M Peloquin; Gautam Goel; Lingjia Kong; Hailiang Huang; Talin Haritunians; R Balfour Sartor; Mark J Daly; Rodney D Newberry; Dermot P McGovern; Vijay Yajnik; Sergio A Lira; Ramnik J Xavier
Journal:  JCI Insight       Date:  2016-08-18

10.  GWAS and network analysis of co-occurring nicotine and alcohol dependence identifies significantly associated alleles and network.

Authors:  Bo Xiang; Bao-Zhu Yang; Hang Zhou; Henry Kranzler; Joel Gelernter
Journal:  Am J Med Genet B Neuropsychiatr Genet       Date:  2018-11-28       Impact factor: 3.568
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