Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations

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Fältnamn	Indikatorer	Metadata
000		05738naa a2200925 4500
001		oai:DiVA.org:uu-171674
003		SwePub
008		120325s2012 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1716742 URI
024	7	a https://doi.org/10.1371/journal.pgen.10024902 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Demirkan, Ayse4 aut
245	1 0	a Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations
264		c 2012-02-16
264	1	b Public Library of Science (PLoS),c 2012
338		a electronic2 rdacarrier
520		a Phospho- 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 x 10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10 x 10(-57)). After a correction for multiple comparisons (P-value, 2.2 x 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.
700	1	a van Duijn, Cornelia M.4 aut
700	1	a Ugocsai, Peter4 aut
700	1	a Isaacs, Aaron4 aut
700	1	a Pramstaller, Peter P.4 aut
700	1	a Liebisch, Gerhard4 aut
700	1	a Wilson, James F.4 aut
700	1	a Johansson, Åsau Uppsala universitet,Genomik4 aut0 (Swepub:uu)asjoh108
700	1	a Rudan, Igor4 aut
700	1	a Aulchenko, Yurii S.4 aut
700	1	a Kirichenko, Anatoly V.4 aut
700	1	a Janssens, A. Cecile J. W.4 aut
700	1	a Jansen, Ritsert C.4 aut
700	1	a Gnewuch, Carsten4 aut
700	1	a Domingues, Francisco S.4 aut
700	1	a Pattaro, Cristian4 aut
700	1	a Wild, Sarah H.4 aut
700	1	a Jonasson, Ingeru Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut0 (Swepub:uu)ingejona
700	1	a Polasek, Ozren4 aut
700	1	a Zorkoltseva, Irina V.4 aut
700	1	a Hofman, Albert4 aut
700	1	a Karssen, Lennart C.4 aut
700	1	a Struchalin, Maksim4 aut
700	1	a Floyd, James4 aut
700	1	a Igl, Wilmar4 aut
700	1	a Biloglav, Zrinka4 aut
700	1	a Broer, Linda4 aut
700	1	a Pfeufer, Arne4 aut
700	1	a Pichler, Irene4 aut
700	1	a Campbell, Susan4 aut
700	1	a Zaboli, Ghazalu Uppsala universitet,Institutionen för immunologi, genetik och patologi4 aut
700	1	a Kolcic, Ivana4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Huffman, Jennifer4 aut
700	1	a Hastie, Nicholas D.4 aut
700	1	a Uitterlinden, Andre4 aut
700	1	a Franke, Lude4 aut
700	1	a Franklin, Christopher S.4 aut
700	1	a Vitart, Veronique4 aut
700	1	a Nelson, Christopher P.4 aut
700	1	a Preuss, Michael4 aut
700	1	a Bis, Joshua C.4 aut
700	1	a O'Donnell, Christopher J.4 aut
700	1	a Franceschini, Nora4 aut
700	1	a Witteman, Jacqueline C. M.4 aut
700	1	a Axenovich, Tatiana4 aut
700	1	a Oostra, Ben A.4 aut
700	1	a Meitinger, Thomas4 aut
700	1	a Hicks, Andrew A.4 aut
700	1	a Hayward, Caroline4 aut
700	1	a Wright, Alan F.4 aut
700	1	a Gyllensten, Ulfu Uppsala universitet,Genomik4 aut0 (Swepub:uu)ulfgyll
700	1	a Campbell, Harry4 aut
700	1	a Schmitz, Gerd4 aut
710	2	a Uppsala universitetb Genomik4 org
773	0	t PLoS Geneticsd : Public Library of Science (PLoS)g 8:2, s. e1002490-q 8:2<e1002490-x 1553-7390x 1553-7404
856	4	u https://uu.diva-portal.org/smash/get/diva2:512140/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4	u https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1002490&type=printable
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-171674
856	4 8	u https://doi.org/10.1371/journal.pgen.1002490

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Av författaren/redakt...: Demirkan, Ayse; van Duijn, Corne ...; Ugocsai, Peter; Isaacs, Aaron; Pramstaller, Pet ...; Liebisch, Gerhar ...; visa fler...; Wilson, James F.; Johansson, Åsa; Rudan, Igor; Aulchenko, Yurii ...; Kirichenko, Anat ...; Janssens, A. Cec ...; Jansen, Ritsert ...; Gnewuch, Carsten; Domingues, Franc ...; Pattaro, Cristia ...; Wild, Sarah H.; Jonasson, Inger; Polasek, Ozren; Zorkoltseva, Iri ...; Hofman, Albert; Karssen, Lennart ...; Struchalin, Maks ...; Floyd, James; Igl, Wilmar; Biloglav, Zrinka; Broer, Linda; Pfeufer, Arne; Pichler, Irene; Campbell, Susan; Zaboli, Ghazal; Kolcic, Ivana; Rivadeneira, Fer ...; Huffman, Jennife ...; Hastie, Nicholas ...; Uitterlinden, An ...; Franke, Lude; Franklin, Christ ...; Vitart, Veroniqu ...; Nelson, Christop ...; Preuss, Michael; Bis, Joshua C.; O'Donnell, Chris ...; Franceschini, No ...; Witteman, Jacque ...; Axenovich, Tatia ...; Oostra, Ben A.; Meitinger, Thoma ...; Hicks, Andrew A.; Hayward, Carolin ...; Wright, Alan F.; Gyllensten, Ulf; Campbell, Harry; Schmitz, Gerd; visa färre...

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