A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease

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Fältnamn	Indikatorer	Metadata
000		07096naa a2201489 4500
001		oai:lup.lub.lu.se:86ac4894-f029-4fcc-adae-61499537b83b
003		SwePub
008		160401s2011 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:DiVA.org:umu-47670
024	7	a https://lup.lub.lu.se/record/21871592 URI
024	7	a https://doi.org/10.1161/CIRCGENETICS.110.9587282 DOI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-476702 URI
040		a (SwePub)lud (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Wild, Philipp S.4 aut
245	1 0	a A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease
264	1	b American Heart Association/Lippincott, Williams & Wilkins,c 2011
520		a 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). Methods and 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 x 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 x 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 x 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. (Circ Cardiovasc Genet. 2011;4:403-412.)
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653		a coronary artery disease
653		a genome-wide association studies
653		a gene
653		a expression
653		a genetic variation
653		a genomics
653		a eQTL
653		a eSNP
653		a LIPA
653		a coronary artery disease
700	1	a Zeller, Tanja4 aut
700	1	a Schillert, Arne4 aut
700	1	a Szymczak, Silke4 aut
700	1	a Sinning, Christoph R.4 aut
700	1	a Deiseroth, Arne4 aut
700	1	a Schnabel, Renate B.4 aut
700	1	a Lubos, Edith4 aut
700	1	a Keller, Till4 aut
700	1	a Eleftheriadis, Medea S.4 aut
700	1	a Bickel, Christoph4 aut
700	1	a Rupprecht, Hans J.4 aut
700	1	a Wilde, Sandra4 aut
700	1	a Rossmann, Heidi4 aut
700	1	a Diemert, Patrick4 aut
700	1	a Cupples, L. Adrienne4 aut
700	1	a Perret, Claire4 aut
700	1	a Erdmann, Jeanette4 aut
700	1	a Stark, Klaus4 aut
700	1	a Kleber, Marcus E.4 aut
700	1	a Epstein, Stephen E.4 aut
700	1	a Voight, Benjamin F.4 aut
700	1	a Kuulasmaa, Kari4 aut
700	1	a Li, Mingyao4 aut
700	1	a Schaefer, Arne S.4 aut
700	1	a Klopp, Norman4 aut
700	1	a Braund, Peter S.4 aut
700	1	a Sager, Hendrik4 aut
700	1	a Demissie, Serkalem4 aut
700	1	a Proust, Carole4 aut
700	1	a Koenig, Inke R.4 aut
700	1	a Wichmann, Heinz-Erich4 aut
700	1	a Reinhard, Wibke4 aut
700	1	a Hoffmann, Michael M.4 aut
700	1	a Virtamo, Jarmo4 aut
700	1	a Burnett, Mary Susan4 aut
700	1	a Siscovick, David4 aut
700	1	a Wiklund, Per Gunnaru Umeå universitet,Medicin4 aut0 (Swepub:umu)pewi0010
700	1	a Qu, Liming4 aut
700	1	a El Mokthari, Nour Eddine4 aut
700	1	a Thompson, John R.4 aut
700	1	a Peters, Annette4 aut
700	1	a Smith, Albert V.4 aut
700	1	a Yon, Emmanuelle4 aut
700	1	a Baumert, Jens4 aut
700	1	a Hengstenberg, Christian4 aut
700	1	a Maerz, Winfried4 aut
700	1	a Amouyel, Philippe4 aut
700	1	a Devaney, Joseph4 aut
700	1	a Schwartz, Stephen4 aut
700	1	a Saarela, Olli4 aut
700	1	a Mehta, Nehal N.4 aut
700	1	a Rubin, Diana4 aut
700	1	a Silander, Kaisa4 aut
700	1	a Hall, Alistair S.4 aut
700	1	a Ferriers, Jean4 aut
700	1	a Harris, Tamara B.4 aut
700	1	a Melander, Olleu Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups4 aut0 (Swepub:lu)endo-ome
700	1	a Kee, Frank4 aut
700	1	a Hakonarson, Hakon4 aut
700	1	a Schrezenmeir, Juergen4 aut
700	1	a Gudnason, Vilmundur4 aut
700	1	a Elosua, Roberto4 aut
700	1	a Arveiler, Dominique4 aut
700	1	a Evans, Alun4 aut
700	1	a Rader, Daniel J.4 aut
700	1	a Illig, Thomas4 aut
700	1	a Schreiber, Stefan4 aut
700	1	a Bis, Joshua C.4 aut
700	1	a Altshuler, David4 aut
700	1	a Kavousi, Maryam4 aut
700	1	a Witteman, Jaqueline C. M.4 aut
700	1	a Uitterlinden, Andre G.4 aut
700	1	a Hofman, Albert4 aut
700	1	a Folsom, Aaron R.4 aut
700	1	a Barbalic, Maja4 aut
700	1	a Boerwinkle, Eric4 aut
700	1	a Kathiresan, Sekar4 aut
700	1	a Reilly, Muredach P.4 aut
700	1	a O'Donnell, Christopher J.4 aut
700	1	a Samani, Nilesh J.4 aut
700	1	a Schunkert, Heribert4 aut
700	1	a Cambien, Francois4 aut
700	1	a Lackner, Karl J.4 aut
700	1	a Tiret, Laurence4 aut
700	1	a Salomaa, Veikko4 aut
700	1	a Munzel, Thomas4 aut
700	1	a Ziegler, Andreas4 aut
700	1	a Blankenberg, Stefan4 aut
710	2	a Umeå universitetb Medicin4 org
773	0	t Circulation: Cardiovascular Geneticsd : American Heart Association/Lippincott, Williams & Wilkinsg 4:4, s. 203-403q 4:4<203-403x 1942-325Xx 1942-3268
856	4	u http://dx.doi.org/10.1161/CIRCGENETICS.110.958728x freey FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/2187159
856	4 8	u https://doi.org/10.1161/CIRCGENETICS.110.958728
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-47670

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Av författaren/redakt...: Wild, Philipp S.; Zeller, Tanja; Schillert, Arne; Szymczak, Silke; Sinning, Christo ...; Deiseroth, Arne; visa fler...; Schnabel, Renate ...; Lubos, Edith; Keller, Till; Eleftheriadis, M ...; Bickel, Christop ...; Rupprecht, Hans ...; Wilde, Sandra; Rossmann, Heidi; Diemert, Patrick; Cupples, L. Adri ...; Perret, Claire; Erdmann, Jeanett ...; Stark, Klaus; Kleber, Marcus E ...; Epstein, Stephen ...; Voight, Benjamin ...; Kuulasmaa, Kari; Li, Mingyao; Schaefer, Arne S ...; Klopp, Norman; Braund, Peter S.; Sager, Hendrik; Demissie, Serkal ...; Proust, Carole; Koenig, Inke R.; Wichmann, Heinz- ...; Reinhard, Wibke; Hoffmann, Michae ...; Virtamo, Jarmo; Burnett, Mary Su ...; Siscovick, David; Wiklund, Per Gun ...; Qu, Liming; El Mokthari, Nou ...; Thompson, John R ...; Peters, Annette; Smith, Albert V.; Yon, Emmanuelle; Baumert, Jens; Hengstenberg, Ch ...; Maerz, Winfried; Amouyel, Philipp ...; Devaney, Joseph; Schwartz, Stephe ...; Saarela, Olli; Mehta, Nehal N.; Rubin, Diana; Silander, Kaisa; Hall, Alistair S ...; Ferriers, Jean; Harris, Tamara B ...; Melander, Olle; Kee, Frank; Hakonarson, Hako ...; Schrezenmeir, Ju ...; Gudnason, Vilmun ...; Elosua, Roberto; Arveiler, Domini ...; Evans, Alun; Rader, Daniel J.; Illig, Thomas; Schreiber, Stefa ...; Bis, Joshua C.; Altshuler, David; Kavousi, Maryam; Witteman, Jaquel ...; Uitterlinden, An ...; Hofman, Albert; Folsom, Aaron R.; Barbalic, Maja; Boerwinkle, Eric; Kathiresan, Seka ...; Reilly, Muredach ...; O'Donnell, Chris ...; Samani, Nilesh J ...; Schunkert, Herib ...; Cambien, Francoi ...; Lackner, Karl J.; Tiret, Laurence; Salomaa, Veikko; Munzel, Thomas; Ziegler, Andreas; Blankenberg, Ste ...; visa färre...

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