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dc.contributor.authorDemirkan, Ayşe
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorUgocsai, Peter
dc.contributor.authorIsaacs, Aaron
dc.contributor.authorPramstaller, Peter P.
dc.contributor.authorLiebisch, Gerhard
dc.contributor.authorWilson, James F.
dc.contributor.authorJohansson, Åsa
dc.contributor.authorRudan, Igor
dc.contributor.authorAulchenko, Yurii S.
dc.contributor.authorKirichenko, Anatoly V.
dc.contributor.authorJanssens, A. Cecile J. W.
dc.contributor.authorJansen, Ritsert C.
dc.contributor.authorGnewuch, Carsten
dc.contributor.authorDomingues, Francisco S.
dc.contributor.authorPattaro, Cristian
dc.contributor.authorWild, Sarah H.
dc.contributor.authorJonasson, Inger
dc.contributor.authorPolasek, Ozren
dc.contributor.authorZorkoltseva, Irina V.
dc.contributor.authorKarssen, Lennart C.
dc.contributor.authorStruchalin, Maksim
dc.contributor.authorFloyd, James
dc.contributor.authorIgl, Wilmar
dc.contributor.authorBiloglav, Zrinka
dc.contributor.authorBroer, Linda
dc.contributor.authorPfeufer, Arne
dc.contributor.authorPichler, Irene
dc.contributor.authorZaboli, Ghazal
dc.contributor.authorKolcic, Ivana
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorHuffman, Jennifer
dc.contributor.authorHastie, Nicholas D.
dc.contributor.authorUitterlinden, Andre
dc.contributor.authorFranke, Lude
dc.contributor.authorVitart, Veronique
dc.contributor.authorNelson, Christopher P.
dc.contributor.authorPreuss, Michael
dc.contributor.authorBis, Joshua C.
dc.contributor.authorFranceschini, Nora
dc.contributor.authorWitteman, Jacqueline C. M.
dc.contributor.authorAxenovich, Tatiana
dc.contributor.authorOostra, Ben A.
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorHicks, Andrew A.
dc.contributor.authorHayward, Caroline
dc.contributor.authorWright, Alan F.
dc.contributor.authorGyllensten, Ulf
dc.contributor.authorCampbell, Harry
dc.contributor.authorSchmitz, Gerd
dc.contributor.authorHofman, Albert
dc.contributor.authorCampbell, Susanna Grace
dc.contributor.authorFranklin, Christopher S.
dc.contributor.authorO'Donnell, Christopher Joseph
dc.date.accessioned2012-04-03T17:07:12Z
dc.date.issued2012
dc.identifier.citationDemirkan, Ayşe, Cornelia M. van Duijn, Peter Ugocsai, Aaron Isaacs, Peter P. Pramstaller, Gerhard Liebisch, James F. Wilson, et al. 2012. Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations. PLoS Genetics 8(2): e1002490.en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:8496567
dc.description.abstractPhospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids \((smallest P-value = 9.88×10^{−204})\) and 10 loci for sphingolipids \((smallest P-value = 3.10 \times 10^{-57})\). After a correction for multiple comparisons \((P-value<2.2×10^{−9})\), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pgen.1002490en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3280968/pdf/en_US
dash.licenseLAA
dc.subjectbiologyen_US
dc.subjectbiochemistryen_US
dc.subjectlipidsen_US
dc.subjectmetabolismen_US
dc.subjectgeneticsen_US
dc.subjecthuman geneticsen_US
dc.subjectepidemiologyen_US
dc.subjectmedicineen_US
dc.titleGenome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrationsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Geneticsen_US
dash.depositing.authorO'Donnell, Christopher Joseph
dc.date.available2012-04-03T17:07:12Z
dc.identifier.doi10.1371/journal.pgen.1002490*
dash.authorsorderedfalse
dash.contributor.affiliatedCampbell, Susanna Grace
dash.contributor.affiliatedO'Donnell, Christopher
dash.contributor.affiliatedHofman, Albert


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