Genome-wide association study identifies novel loci associated with circulating phospho- and sphingolipid concentrations

DIAGRAM Consortium, Ayşe Demirkan, Cornelia M van Duijn, Peter Ugocsai, Aaron Isaacs, Peter P Pramstaller, Gerhard Liebisch, James F Wilson, Åsa Johansson, Igor Rudan, Yurii S Aulchenko, Anatoly V Kirichenko, A Cecile J W Janssens, Ritsert C Jansen, Carsten Gnewuch, Francisco S Domingues, Cristian Pattaro, Sarah H Wild, Inger Jonasson, Ozren PolasekIrina V Zorkoltseva, Albert Hofman, Lennart C Karssen, Maksim Struchalin, James Floyd, Wilmar Igl, Zrinka Biloglav, Linda Broer, Arne Pfeufer, Irene Pichler, Susan Campbell, Ghazal Zaboli, Ivana Kolcic, Fernando Rivadeneira, Jennifer Huffman, Nicholas D Hastie, Andre Uitterlinden, Lude Franke, Christopher S Franklin, Veronique Vitart, Christopher P Nelson, Michael Preuss, Joshua C Bis, Christopher J O'Donnell, Nora Franceschini, Jacqueline C M Witteman, Tatiana Axenovich, Ben A Oostra, Caroline Hayward, Alan F Wright, Harry Campbell

Research output: Contribution to journalArticlepeer-review

Abstract

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 = 9.88×10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10×10(-57)). After a correction for multiple comparisons (P-value
Original languageEnglish
Pages (from-to)e1002490
JournalPLoS Genetics
Volume8
Issue number2
DOIs
Publication statusPublished - 2012

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