Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
24013639
TITLE
Systematic identification of trans eQTLs as putative drivers of known disease associations.
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.
DATE PUBLISHED
2013 Oct
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/12/24
accepted 2013/08/14
aheadofprint 2013/09/08
entrez 2013/09/10 06:00
pubmed 2013/09/10 06:00
medline 2013/11/19 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Westra HJ Westra Harm-Jan HJ 1] Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. [2].
Peters MJ Peters Marjolein J MJ
Esko T Esko Tõnu T
Yaghootkar H Yaghootkar Hanieh H
Schurmann C Schurmann Claudia C
Kettunen J Kettunen Johannes J
Christiansen MW Christiansen Mark W MW
Fairfax BP Fairfax Benjamin P BP
Schramm K Schramm Katharina K
Powell JE Powell Joseph E JE
Zhernakova A Zhernakova Alexandra A
Zhernakova DV Zhernakova Daria V DV
Veldink JH Veldink Jan H JH
Van den Berg LH Van den Berg Leonard H LH
Karjalainen J Karjalainen Juha J
Withoff S Withoff Sebo S
Uitterlinden AG Uitterlinden André G AG
Hofman A Hofman Albert A
Rivadeneira F Rivadeneira Fernando F
't Hoen PA 't Hoen Peter A C PA
Reinmaa E Reinmaa Eva E
Fischer K Fischer Krista K
Nelis M Nelis Mari M
Milani L Milani Lili L
Melzer D Melzer David D
Ferrucci L Ferrucci Luigi L
Singleton AB Singleton Andrew B AB
Hernandez DG Hernandez Dena G DG
Nalls MA Nalls Michael A MA
Homuth G Homuth Georg G
Nauck M Nauck Matthias M
Radke D Radke Dörte D
Völker U Völker Uwe U
Perola M Perola Markus M
Salomaa V Salomaa Veikko V
Brody J Brody Jennifer J
Suchy-Dicey A Suchy-Dicey Astrid A
Gharib SA Gharib Sina A SA
Enquobahrie DA Enquobahrie Daniel A DA
Lumley T Lumley Thomas T
Montgomery GW Montgomery Grant W GW
Makino S Makino Seiko S
Prokisch H Prokisch Holger H
Herder C Herder Christian C
Roden M Roden Michael M
Grallert H Grallert Harald H
Meitinger T Meitinger Thomas T
Strauch K Strauch Konstantin K
Li Y Li Yang Y
Jansen RC Jansen Ritsert C RC
Visscher PM Visscher Peter M PM
Knight JC Knight Julian C JC
Psaty BM Psaty Bruce M BM
Ripatti S Ripatti Samuli S
Teumer A Teumer Alexander A
Frayling TM Frayling Timothy M TM
Metspalu A Metspalu Andres A
van Meurs JB van Meurs Joyce B J JB
Franke L Franke Lude L
INVESTIGATORS
JOURNAL
VOLUME: 45
ISSUE: 10
TITLE: Nature genetics
ISOABBREVIATION: Nat. Genet.
YEAR: 2013
MONTH: Oct
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nat Genet. 2011 Jun;43(6):561-4 21572415
Cites PLoS Genet. 2010 Apr;6(4):e1000888 20369019
Cites Bioinformatics. 2011 Aug 1;27(15):2104-11 21653519
Cites PLoS Genet. 2011 Aug;7(8):e1002197 21829388
Cites PLoS Genet. 2011 Aug;7(8):e1002216 21829393
Cites Eur J Epidemiol. 2011 Aug;26(8):657-86 21877163
Cites Nat Genet. 2011 Oct;43(10):1005-11 21909110
Cites PLoS Genet. 2011 Dec;7(12):e1002367 22144904
Cites Nucleic Acids Res. 2012 Jan;40(Database issue):D930-4 22064851
Cites Nucleic Acids Res. 2012 Jan;40(Database issue):D84-90 22086963
Cites Lupus. 2000;9(9):664-71 11199920
Cites Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2610-5 12604793
Cites J Exp Med. 2003 Mar 17;197(6):711-23 12642603
Cites Nature. 2003 Dec 18;426(6968):789-96 14685227
Cites JAMA. 2004 Oct 6;292(13):1581-7 15467060
Cites Arthritis Rheum. 1982 Apr;25(4):401-6 6176248
Cites Immunogenetics. 1988;27(4):259-64 2894352
Cites JAMA. 1995 Aug 23-30;274(8):620-5 7637142
Cites Nat Genet. 2010 May;42(5):376-84 20383146
Cites Nature. 2010 Aug 5;466(7307):707-13 20686565
Cites PLoS One. 2010;5(8):e11961 20694148
Cites PLoS Genet. 2010 Sep;6(9):e1001113 20844574
Cites Nat Genet. 2009 Jun;41(6):703-7 19430480
Cites Nat Genet. 2009 Jun;41(6):666-76 19430483
Cites Nature. 2010 Sep 23;467(7314):460-4 20827270
Cites Nature. 2010 Oct 28;467(7319):1061-73 20981092
Cites Circ Res. 2011 Mar 4;108(5):534-6 21372290
Cites PLoS Genet. 2011 Feb;7(2):e1002004 21383967
Cites Am J Hum Genet. 2011 May 13;88(5):664-73 21565293
Cites PLoS One. 2012;7(4):e34442 22493691
Cites Nat Genet. 2012 May;44(5):502-10 22446964
Cites PLoS One. 2012;7(4):e35430 22563384
Cites Nat Genet. 2012 Jun;44(6):676-80 22561518
Cites Nucleic Acids Res. 2012 Jul;40(Web Server issue):W65-70 22544707
Cites Nature. 2012 Sep 6;489(7414):57-74 22955616
Cites Nat Genet. 2012 Oct;44(10):1084-9 22941192
Cites Eur J Hum Genet. 2013 Jan;21(1):48-54 22692066
Cites Eur J Hum Genet. 2013 Sep;21(9):994-9 23249952
Cites Immunity. 1996 Dec;5(6):537-49 8986714
Cites Nat Genet. 1998 May;19(1):56-9 9590289
Cites J Evol Biol. 2005 Sep;18(5):1368-73 16135132
Cites Mol Immunol. 2007 Jan;44(1-3):33-43 16908067
Cites PLoS One. 2007;2(7):e622 17637838
Cites Nucleic Acids Res. 2008 Aug;36(13):4417-23 18596082
Cites PLoS Genet. 2008 Oct;4(10):e1000232 18949031
Cites Nat Genet. 2009 Jan;41(1):35-46 19060910
Cites PLoS Genet. 2009 Jan;5(1):e1000338 19148276
Cites Nat Genet. 2009 Mar;41(3):342-7 19198610
Cites Bioinformatics. 2009 Mar 1;25(5):655-61 19098027
Cites Am J Hypertens. 2009 May;22(5):538-44 19265792
Cites Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 19474294
Cites Nucleic Acids Res. 2009 Jul;37(Web Server issue):W600-5 19417063
Cites Nat Genet. 2009 Nov;41(11):1234-7 19838193
Cites Nat Genet. 2009 Nov;41(11):1191-8 19862010
Cites Nat Genet. 2010 Apr;42(4):295-302 20190752
Cites Nature. 2010 Apr 1;464(7289):768-72 20220758
Cites PLoS Genet. 2011 May;7(5):e1002078 21637794
GRANTS
GRANTID AGENCY COUNTRY
090532 Wellcome Trust United Kingdom
G0500070 Medical Research Council United Kingdom
Z99 AG999999 Intramural NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Diabetes Mellitus, Type 1 genetics
Genetic Predisposition to Disease genetics
Humans genetics
Lupus Erythematosus, Systemic genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait Loci genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS571772 NLM
PMC3991562 NLM
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