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PMID: 25597830 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Biological interpretation of genome-wide association studies using predicted gene functions.

Nature communications ·Vol. 6 ·2015-01-19 ·Pages 5890

Pers TH, Karjalainen JM, Chan Y, Westra HJ, Wood AR, Yang J, Lui JC, Vedantam S, Gustafsson S, Esko T, Frayling T, Speliotes EK, Genetic Investigation of ANthropometric Traits GIANT Consortium, Boehnke M, Raychaudhuri S, Fehrmann RS, Hirschhorn JN, Franke L

Abstract

The main challenge for gaining biological insights from genetic associations is identifying which genes and pathways explain the associations. Here we present DEPICT, an integrative tool that employs predicted gene functions to systematically prioritize the most likely causal genes at associated loci, highlight enriched pathways and identify tissues/cell types where genes from associated loci are highly expressed. DEPICT is not limited to genes with established functions and prioritizes relevant gene sets for many phenotypes.

MeSH Terms
Genome-Wide Association Study/methods Software
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Pers Tune H
1] Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA.
Karjalainen Juha M
Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen 9711, The Netherlands.
Chan Yingleong
1] Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Westra Harm-Jan
Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Wood Andrew R
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
Yang Jian
1] Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia [2] The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane, Queensland 4012, Australia.
Lui Julian C
Section on Growth and Development, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Vedantam Sailaja
1] Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA.
Gustafsson Stefan
Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala 75185, Sweden.
Esko Tonu
1] Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA [3] Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
Frayling Tim
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
Speliotes Elizabeth K
Department of Internal Medicine, Division of Gastroenterology, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Genetic Investigation of ANthropometric Traits (GIANT) Consortium
Boehnke Michael
Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA.
Raychaudhuri Soumya
1] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA [2] Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [3] Partners HealthCare Center for Personalized Genetic Medicine, Boston, Massachusetts 02115, USA [4] Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [5] Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PL, UK.
Fehrmann Rudolf S N
Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen 9711, The Netherlands.
Hirschhorn Joel N
1] Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts 02115, USA [2] Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 2142, USA [3] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Franke Lude
Department of Genetics, University of Groningen, University Medical Centre Groningen, Groningen 9711, The Netherlands.
Investigators
444 investigators, click to expand
Wood Andrew R
Esko Tonu
Yang Jian
Vedantam Sailaja
Pers Tune H
Gustafsson Stefan
Chu Audrey Y
Estrada Karol
Luan Jian'an
Kutalik Zoltán
Amin Najaf
Buchkovich Martin L
Croteau-Chonka Damien C
Day Felix R
Duan Yanan
Fall Tove
Fehrmann Rudolf
Ferreira Teresa
Jackson Anne U
Karjalainen Juha
Lo Ken Sin
Locke Adam E
Mägi Reedik
Mihailov Evelin
Porcu Eleonora
Randall Joshua C
Scherag André
Vinkhuyzen Anna A E
Westra Harm-Jan
Winkler Thomas W
Workalemahu Tsegaselassie
Zhao Jing Hua
Absher Devin
Albrecht Eva
Anderson Denise
Baron Jeffrey
Beekman Marian
Demirkan Ayse
Ehret Georg B
Feenstra Bjarke
Feitosa Mary F
Fischer Krista
Fraser Ross M
Goel Anuj
Gong Jian
Justice E
Kanoni Stavroula
Kleber Marcus E
Kristiansson Kati
Lim Unhee
Lotay Vaneet
Lui Julian C
Mangino Massimo
Mateo Leach Irene
Medina-Gomez Carolina
Nalls Michael A
Nyholt Dale R
Palmer Cameron D
Pasko Dorota
Pechlivanis Sonali
Prokopenko Inga
Ried Janina S
Ripke Stephan
Shungin Dmitry
Stancáková Alena
Strawbridge Rona J
Sung Yun Ju
Tanaka Toshiko
Teumer Alexander
Trompet Stella
van der Laan Sander W
van Setten Jessica
Van Vliet-Ostaptchouk Jana V
Wang Zhaoming
Yengo Loïc
Zhang Weihua
Afzal Uzma
Ärnlöv Johan
Arscott Gillian M
Bandinelli Stefania
Barrett Amy
Bellis Claire
Bennett Amanda J
Berne Christian
Blüher Matthias
Bolton Jennifer L
Böttcher Yvonne
Boyd Heather A
Bruinenberg Marcel
Buckley Brendan M
Buyske Steven
Caspersen Ida H
Chines Peter S
Clarke Robert
Claudi-Boehm Simone
Cooper Matthew
Daw E Warwick
De Jong A
Deelen Joris
Delgado Graciela
Denny Josh C
Dhonukshe-Rutten Rosalie
Dimitriou Maria
Doney Alex S F
Dörr Marcus
Eklund Niina
Eury Elodie
Folkersen Lasse
Garcia Melissa E
Geller Frank
Giedraitis Vilmantas
Go Alan S
Grallert Harald
Grammer Tanja B
Gräßler Jürgen
Grönberg Henrik
de Groot Lisette C P G M
Groves Christopher J
Haessler Jeffrey
Haller Toomas
Hallmans Goran
Hannemann Anke
Hartman Catharina A
Hassinen Maija
Hayward Caroline
Heard-Costa Nancy L
Helmer Quinta
Hemani Gibran
Henders Anjali K
Hillege Hans L
Hlatky Mark A
Hoffmann Wolfgang
Hoffmann Per
Holmen Oddgeir
Houwing-Duistermaat Jeanine J
Illig Thomas
Isaacs Aaron
James Alan L
Jeff Janina
Johansen Berit
Johansson Åsa
Jolley Jennifer
Juliusdottir Thorhildur
Junttila Juhani
Kho Abel N
Kinnunen Leena
Klopp Norman
Kocher Thomas
Kratzer Wolfgang
Lichtner Peter
Lind Lars
Lindström Jaana
Lobbens Stéphane
Lorentzon Mattias
Lu Yingchang
Lyssenko Valeriya
Magnusson Patrik K E
Mahajan Anubha
Maillard Marc
McArdle Wendy L
McKenzie Colin A
McLachlan Stela
McLaren Paul J
Menni Cristina
Merger Sigrun
Milani Lili
Moayyeri Alireza
Monda Keri L
Morken Mario A
Müller Gabriele
Müller-Nurasyid Martina
Musk Arthur W
Narisu Narisu
Nauck Matthias
Nolte Ilja M
Nöthen Markus M
Oozageer Laticia
Pilz Stefan
Rayner Nigel W
Renstrom Frida
Robertson Neil R
Rose Lynda M
Roussel Ronan
Sanna Serena
Scharnagl Hubert
Scholtens Salome
Schumacher Fredrick R
Schunkert Heribert
Scott Robert A
Sehmi Joban
Seufferlein Thomas
Shi Jianxin
Silventoinen Karri
Smit Johannes H
Smith Albert Vernon
Smolonska Joanna
Stanton Alice V
Stirrups Kathleen
Stott David J
Stringham Heather M
Sundström Johan
Swertz Morris A
Syvänen Ann-Christine
Tayo Bamidele O
Thorleifsson Gudmar
Tyrer Jonathan P
van Dijk Suzanne
van Schoor Natasja M
van der Velde Nathalie
van Heemst Diana
van Oort Floor V A
Vermeulen Sita H
Verweij Niek
Vonk Judith M
Waite Lindsay L
Waldenberger Melanie
Wennauer Roman
Wilkens Lynne R
Willenborg Christina
Wilsgaard Tom
Wojczynski Mary K
Wong Andrew
Wright Alan F
Zhang Qunyuan
Arveiler Dominique
Bakker Stephan J L
Beilby John
Bergman Richard N
Bergmann Sven
Biffar Reiner
Blangero John
Boomsma I
Bornstein Stefan R
Bovet Pascal
Brambilla Paolo
Brown Morris J
Campbell Harry
Caulfield Mark J
Chakravarti Aravinda
Collins Rory
Collins Francis S
Crawford Dana C
Cupples L Adrienne
Danesh John
de Faire Ulf
den Ruijter Hester M
Erbel Raimund
Erdmann Jeanette
Eriksson Johan G
Farrall Martin
Ferrannini Ele
Ferrières Jean
Ford Ian
Forouhi Nita G
Forrester Terrence
Gansevoort Ron T
Gejman Pablo V
Gieger Christian
Golay Alain
Gottesman Omri
Gudnason Vilmundur
Gyllensten Ulf
Haas David W
Hall Alistair S
Harris Tamara B
Hattersley Andrew T
Heath Andrew C
Hengstenberg Christian
Hicks Andrew A
Hindorff Lucia A
Hingorani Aroon D
Hofman Albert
Hovingh G Kees
Humphries Steve E
Hunt Steven C
Hypponen Elina
Jacobs Kevin B
Jarvelin Marjo-Riitta
Jousilahti Pekka
Jula Antti M
Kaprio Jaakko
Kastelein John J P
Kayser Manfred
Kee Frank
Keinanen-Kiukaanniemi Sirkka M
Kiemeney Lambertus A
Kooner Jaspal S
Kooperberg Charles
Koskinen Seppo
Kovacs Peter
Kraja Aldi T
Kumari Meena
Kuusisto Johanna
Lakka Timo A
Langenberg Claudia
Le Marchand Loic
Lehtimäki Terho
Lupoli Sara
Madden Pamela A F
Männistö Satu
Manunta Paolo
Marette André
Matise Tara C
McKnight Barbara
Meitinger Thomas
Moll Frans L
Montgomery Grant W
Morris Andrew D
Morris Andrew P
Murray Jeffrey C
Nelis Mari
Ohlsson Claes
Oldehinkel Albertine J
Ong Ken K
Ouwehand Willem H
Pasterkamp Gerard
Peters Annette
Pramstaller Peter P
Price Jackie F
Qi Lu
Raitakari Olli T
Rankinen Tuomo
Rao D C
Rice Treva K
Ritchie Marylyn
Rudan Igor
Salomaa Veikko
Samani Nilesh J
Saramies Jouko
Sarzynski Mark A
Schwarz Peter E H
Sebert Sylvain
Sever Peter
Shuldiner Alan R
Sinisalo Juha
Steinthorsdottir Valgerdur
Stolk Ronald P
Tardif Jean-Claude
Tönjes Anke
Tremblay Angelo
Tremoli Elena
Virtamo Jarmo
Vohl Marie-Claude
Amouyel Philippe
Asselbergs Folkert W
Assimes Themistocles L
Bochud Murielle
Boehm Bernhard O
Boerwinkle Eric
Bottinger Erwin P
Bouchard Claude
Cauchi Stéphane
Chambers John C
Chanock Stephen J
Cooper Richard S
de Bakker Paul I W
Dedoussis George
Ferrucci Luigi
Franks Paul W
Froguel Philippe
Groop Leif C
Haiman Christopher A
Hamsten Anders
Hayes M Geoffrey
Hui Jennie
Hunter David J
Hveem Kristian
Jukema J Wouter
Kaplan Robert C
Kivimaki Mika
Kuh Diana
Laakso Markku
Liu Yongmei
Martin Nicholas G
März Winfried
Melbye Mads
Moebus Susanne
Munroe Patricia B
Njølstad Inger
Oostra Ben A
Palmer Colin N A
Pedersen Nancy L
Perola Markus
Pérusse Louis
Peters Ulrike
Powell Joseph E
Power Chris
Quertermous Thomas
Rauramaa Rainer
Reinmaa Eva
Ridker Paul M
Rivadeneira Fernando
Rotter Jerome I
Saaristo Timo E
Saleheen Danish
Schlessinger David
Slagboom P Eline
Snieder Harold
Spector Tim D
Strauch Konstantin
Stumvoll Michael
Tuomilehto Jaakko
Uusitupa Matti
van der Harst Pim
Völzke Henry
Walker Mark
Wareham Nicholas J
Watkins Hugh
Wichmann H-Erich
Wilson James F
Zanen Pieter
Deloukas Panos
Heid Iris M
Lindgren Cecilia M
Mohlke Karen L
Speliotes Elizabeth K
Thorsteinsdottir Unnur
Barroso Inês
Fox Caroline S
North Kari E
Strachan David P
Beckmann Jacques S
Berndt Sonja I
Boehnke Michael
Borecki Ingrid B
McCarthy Mark I
Metspalu Andres
Stefansson Kari
Uitterlinden André G
van Duijn Cornelia M
Franke Lude
Willer Cristen J
Price Alkes L
Lettre Guillaume
Loos Ruth J F
Weedon Michael N
Ingelsson Erik
O'Connell Jeffrey R
Abecasis Goncalo R
Chasman Daniel I
Goddard Michael E
Visscher Peter M
Hirschhorn Joel N
Frayling Timothy M
References (38)
38 references, click to expand
  1. Biological, clinical and population relevance of 95 loci for blood lipids.
    Nature. 2010 Aug 5;466(7307):707-13 PMID: 20686565
  2. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions.
    PLoS Genet. 2009 Jun;5(6):e1000534 PMID: 19557189
  3. New genetic loci link adipose and insulin biology to body fat distribution.
    Nature. 2015 Feb 12;518(7538):187-96 PMID: 25673412
  4. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits.
    PLoS Genet. 2010 Aug;6(8). pii: e1001058. doi: 10.1371/journal.pgen.1001058 PMID: 20714348
  5. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
    Nat Genet. 2000 May;25(1):25-9 PMID: 10802651
  6. A gene atlas of the mouse and human protein-encoding transcriptomes.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7 PMID: 15075390
  7. ROCR: visualizing classifier performance in R.
    Bioinformatics. 2005 Oct 15;21(20):3940-1 PMID: 16096348
  8. Reconstruction of a functional human gene network, with an application for prioritizing positional candidate genes.
    Am J Hum Genet. 2006 Jun;78(6):1011-25 PMID: 16685651
  9. Clustering by passing messages between data points.
    Science. 2007 Feb 16;315(5814):972-6 PMID: 17218491
  10. A human phenome-interactome network of protein complexes implicated in genetic disorders.
    Nat Biotechnol. 2007 Mar;25(3):309-16 PMID: 17344885
  11. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
    Science. 2007 Jun 1;316(5829):1331-6 PMID: 17463246
  12. PLINK: a tool set for whole-genome association and population-based linkage analyses.
    Am J Hum Genet. 2007 Sep;81(3):559-75 PMID: 17701901
  13. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits.
    Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 PMID: 19474294
  14. Integrating common and rare genetic variation in diverse human populations.
    Nature. 2010 Sep 2;467(7311):52-8 PMID: 20811451
  15. Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.
    PLoS Genet. 2010 Sep;6(9):e1001097 PMID: 20838587
  16. Hundreds of variants clustered in genomic loci and biological pathways affect human height.
    Nature. 2010 Oct 14;467(7317):832-8 PMID: 20881960
  17. Analysing biological pathways in genome-wide association studies.
    Nat Rev Genet. 2010 Dec;11(12):843-54 PMID: 21085203
  18. Reactome: a database of reactions, pathways and biological processes.
    Nucleic Acids Res. 2011 Jan;39(Database issue):D691-7 PMID: 21067998
  19. Meta-analysis of heterogeneous data sources for genome-scale identification of risk genes in complex phenotypes.
    Genet Epidemiol. 2011 Jul;35(5):318-32 PMID: 21484861
  20. Prioritizing candidate disease genes by network-based boosting of genome-wide association data.
    Genome Res. 2011 Jul;21(7):1109-21 PMID: 21536720
  21. HAPGEN2: simulation of multiple disease SNPs.
    Bioinformatics. 2011 Aug 15;27(16):2304-5 PMID: 21653516
  22. APCluster: an R package for affinity propagation clustering.
    Bioinformatics. 2011 Sep 1;27(17):2463-4 PMID: 21737437
  23. KEGG for integration and interpretation of large-scale molecular data sets.
    Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14 PMID: 22080510
  24. On the Use of Gene Ontology Annotations to Assess Functional Similarity among Orthologs and Paralogs: A Short Report.
    PLoS Comput Biol. 2012;8(2):e1002386 PMID: 22359495
  25. Computational tools for prioritizing candidate genes: boosting disease gene discovery.
    Nat Rev Genet. 2012 Aug;13(8):523-36 PMID: 22751426
  26. An integrated map of genetic variation from 1,092 human genomes.
    Nature. 2012 Nov 1;491(7422):56-65 PMID: 23128226
  27. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    Nature. 2012 Nov 1;491(7422):119-24 PMID: 23128233
  28. Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height.
    Hum Mol Genet. 2012 Dec 1;21(23):5193-201 PMID: 22914739
  29. A travel guide to Cytoscape plugins.
    Nat Methods. 2012 Nov;9(11):1069-76 PMID: 23132118
  30. NCBI GEO: archive for functional genomics data sets--update.
    Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5 PMID: 23193258
  31. Systematic identification of trans eQTLs as putative drivers of known disease associations.
    Nat Genet. 2013 Oct;45(10):1238-43 PMID: 24013639
  32. Network analysis of GWAS data.
    Curr Opin Genet Dev. 2013 Dec;23(6):602-10 PMID: 24287332
  33. The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D810-7 PMID: 24285300
  34. Ensembl 2014.
    Nucleic Acids Res. 2014 Jan;42(Database issue):D749-55 PMID: 24316576
  35. Genome-wide association analyses identify variants in developmental genes associated with hypospadias.
    Nat Genet. 2014 Sep;46(9):957-63 PMID: 25108383
  36. Defining the role of common variation in the genomic and biological architecture of adult human height.
    Nat Genet. 2014 Nov;46(11):1173-86 PMID: 25282103
  37. A novel common variant in DCST2 is associated with length in early life and height in adulthood.
    Hum Mol Genet. 2015 Feb 15;24(4):1155-68 PMID: 25281659
  38. Gene expression analysis identifies global gene dosage sensitivity in cancer.
    Nat Genet. 2015 Feb;47(2):115-25 PMID: 25581432
Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms6890
Published
2015-01-19
Epub
2015-00-19
Pages
5890
Language
English
Region
England
NLM ID
101528555
PMCID
PMC4420238
Subset
IM
Grants
Medical Research Council · G1001799 · United Kingdom
Chief Scientist Office · CZB/4/672 · United Kingdom
NIDDK NIH HHS · R01 DK075787 · United States
NIGMS NIH HHS · U01 GM092691 · United States
Medical Research Council · MR/N01104X/1 · United Kingdom
Intramural NIH HHS · United States
Wellcome Trust · 098395 · United Kingdom
NIAMS NIH HHS · R01 AR063759 · United States
NIDDK NIH HHS · 2R01DK075787 · United States
NIAMS NIH HHS · UH2 AR067677 · United States
Medical Research Council · MR/K006584/1 · United Kingdom
Medical Research Council · MR/K013351/1 · United Kingdom
NIDDK NIH HHS · P30 DK020572 · United States
NHLBI NIH HHS · R01 HL117078 · United States
NCI NIH HHS · P30 CA071789 · United States
External Links
PubMed source DOI: 10.1038/ncomms6890 PMC Full Text View journal details
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