title: A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease.
abstract: BACKGROUND
  eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD).
  
  
  RESULTS
  In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7×10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3×10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4×10(-3)).
  
  
  CONCLUSIONS
  The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD.
authors: Department of Medicine II, University Medical Center Mainz, Germany.
authors: Philipp S
authors: PS
authors: Wild
authors: Tanja
authors: T
authors: Zeller
authors: Arne
authors: A
authors: Schillert
authors: Silke
authors: S
authors: Szymczak
authors: Christoph R
authors: CR
authors: Sinning
authors: Arne
authors: A
authors: Deiseroth
authors: Renate B
authors: RB
authors: Schnabel
authors: Edith
authors: E
authors: Lubos
authors: Till
authors: T
authors: Keller
authors: Medea S
authors: MS
authors: Eleftheriadis
authors: Christoph
authors: C
authors: Bickel
authors: Hans J
authors: HJ
authors: Rupprecht
authors: Sandra
authors: S
authors: Wilde
authors: Heidi
authors: H
authors: Rossmann
authors: Patrick
authors: P
authors: Diemert
authors: L Adrienne
authors: LA
authors: Cupples
authors: Claire
authors: C
authors: Perret
authors: Jeanette
authors: J
authors: Erdmann
authors: Klaus
authors: K
authors: Stark
authors: Marcus E
authors: ME
authors: Kleber
authors: Stephen E
authors: SE
authors: Epstein
authors: Benjamin F
authors: BF
authors: Voight
authors: Kari
authors: K
authors: Kuulasmaa
authors: Mingyao
authors: M
authors: Li
authors: Arne S
authors: AS
authors: Schäfer
authors: Norman
authors: N
authors: Klopp
authors: Peter S
authors: PS
authors: Braund
authors: Hendrik B
authors: HB
authors: Sager
authors: Serkalem
authors: S
authors: Demissie
authors: Carole
authors: C
authors: Proust
authors: Inke R
authors: IR
authors: König
authors: Heinz-Erich
authors: HE
authors: Wichmann
authors: Wibke
authors: W
authors: Reinhard
authors: Michael M
authors: MM
authors: Hoffmann
authors: Jarmo
authors: J
authors: Virtamo
authors: Mary Susan
authors: MS
authors: Burnett
authors: David
authors: D
authors: Siscovick
authors: Per Gunnar
authors: PG
authors: Wiklund
authors: Liming
authors: L
authors: Qu
authors: Nour Eddine
authors: NE
authors: El Mokthari
authors: John R
authors: JR
authors: Thompson
authors: Annette
authors: A
authors: Peters
authors: Albert V
authors: AV
authors: Smith
authors: Emmanuelle
authors: E
authors: Yon
authors: Jens
authors: J
authors: Baumert
authors: Christian
authors: C
authors: Hengstenberg
authors: Winfried
authors: W
authors: März
authors: Philippe
authors: P
authors: Amouyel
authors: Joseph
authors: J
authors: Devaney
authors: Stephen M
authors: SM
authors: Schwartz
authors: Olli
authors: O
authors: Saarela
authors: Nehal N
authors: NN
authors: Mehta
authors: Diana
authors: D
authors: Rubin
authors: Kaisa
authors: K
authors: Silander
authors: Alistair S
authors: AS
authors: Hall
authors: Jean
authors: J
authors: Ferrieres
authors: Tamara B
authors: TB
authors: Harris
authors: Olle
authors: O
authors: Melander
authors: Frank
authors: F
authors: Kee
authors: Hakon
authors: H
authors: Hakonarson
authors: Juergen
authors: J
authors: Schrezenmeir
authors: Vilmundur
authors: V
authors: Gudnason
authors: Roberto
authors: R
authors: Elosua
authors: Dominique
authors: D
authors: Arveiler
authors: Alun
authors: A
authors: Evans
authors: Daniel J
authors: DJ
authors: Rader
authors: Thomas
authors: T
authors: Illig
authors: Stefan
authors: S
authors: Schreiber
authors: Joshua C
authors: JC
authors: Bis
authors: David
authors: D
authors: Altshuler
authors: Maryam
authors: M
authors: Kavousi
authors: Jaqueline C M
authors: JC
authors: Witteman
authors: Andre G
authors: AG
authors: Uitterlinden
authors: Albert
authors: A
authors: Hofman
authors: Aaron R
authors: AR
authors: Folsom
authors: Maja
authors: M
authors: Barbalic
authors: Eric
authors: E
authors: Boerwinkle
authors: Sekar
authors: S
authors: Kathiresan
authors: Muredach P
authors: MP
authors: Reilly
authors: Christopher J
authors: CJ
authors: O'Donnell
authors: Nilesh J
authors: NJ
authors: Samani
authors: Heribert
authors: H
authors: Schunkert
authors: Francois
authors: F
authors: Cambien
authors: Karl J
authors: KJ
authors: Lackner
authors: Laurence
authors: L
authors: Tiret
authors: Veikko
authors: V
authors: Salomaa
authors: Thomas
authors: T
authors: Munzel
authors: Andreas
authors: A
authors: Ziegler
authors: Stefan
authors: S
authors: Blankenberg
references: Science. 2007 Jun 8;316(5830):1488-91
references: 17478681
references: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references: 3344216
references: Circulation. 2010 Jun 8;121(22):2388-97
references: 20497981
references: N Engl J Med. 2007 Aug 2;357(5):443-53
references: 17634449
references: J Clin Invest. 1993 Dec;92(6):2713-8
references: 8254026
references: Stat Med. 2009 Dec 20;28(29):3581-96
references: 19691035
references: Ann Med. 2008;40(3):180-96
references: 18382884
references: Nature. 2007 Jun 7;447(7145):661-78
references: 17554300
references: PLoS Genet. 2010 Apr 01;6(4):e1000895
references: 20369022
references: Nat Genet. 2009 Mar;41(3):280-2
references: 19198612
references: Nat Genet. 2008 Feb;40(2):189-97
references: 18193044
references: Genet Epidemiol. 2009;33 Suppl 1:S45-50
references: 19924716
references: Genomics. 1996 Apr 1;33(1):85-93
references: 8617513
references: Nucleic Acids Res. 2010 Jan;38(3):e17
references: 19923232
references: Nature. 2008 Mar 27;452(7186):423-8
references: 18344981
references: Nat Genet. 2009 Mar;41(3):334-41
references: 19198609
references: Nat Rev Genet. 2009 Mar;10(3):184-94
references: 19223927
references: Genomics. 1993 Jan;15(1):245-7
references: 8432549
references: J Biol Chem. 1991 Nov 25;266(33):22479-84
references: 1718995
references: Nat Genet. 2007 Oct;39(10):1217-24
references: 17873874
references: PLoS One. 2010 May 18;5(5):e10693
references: 20502693
references: Science. 2007 Feb 9;315(5813):848-53
references: 17289997
references: Science. 2007 Jun 8;316(5830):1491-3
references: 17478679
references: Eur Heart J. 2010 Apr;31(8):918-25
references: 20219748
references: Nat Genet. 2007 Oct;39(10):1202-7
references: 17873877
references: Thromb Haemost. 2004 Apr;91(4):639-45
references: 15045123
references: Bioinformatics. 2007 May 15;23(10):1294-6
references: 17384015
references: J Biochem. 2006 Jul;140(1):23-38
references: 16877765
references: Am J Pathol. 1984 Feb;114(2):201-8
references: 6198918
references: Nature. 2010 Aug 5;466(7307):714-9
references: 20686566
references: Lancet. 2004 Sep 11-17;364(9438):937-52
references: 15364185
references: J Exp Med. 1995 Dec 1;182(6):1959-71
references: 7500042
references: N Engl J Med. 2003 Oct 23;349(17):1605-13
references: 14573732