Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations
| Autor: | Andrew A. Hicks, Irina V. Zorkoltseva, Christopher S. Franklin, Thomas Meitinger, Michael Preuss, Cristian Pattaro, Lennart C. Karssen, Veronique Vitart, Sarah H. Wild, Fernando Rivadeneira, Åsa Johansson, James F. Wilson, Anatoly V. Kirichenko, Ghazal Zaboli, Ozren Polasek, Wilmar Igl, Tatiana I. Axenovich, Christopher J. O'Donnell, Jacqueline C. M. Witteman, James A B Floyd, Linda Broer, Arne Pfeufer, Lude Franke, Igor Rudan, Zrinka Biloglav, Christopher P. Nelson, Nora Franceschini, Ivana Kolcic, Aaron Isaacs, Yurii S. Aulchenko, Harry Campbell, Nicholas D. Hastie, Cornelia M. van Duijn, Ritsert C. Jansen, Irene Pichler, Alan F. Wright, Caroline Hayward, Albert Hofman, Ben A. Oostra, Jennifer E. Huffman, Ulf Gyllensten, Gerd Schmitz, Carsten Gnewuch, Inger Jonasson, Francisco S. Domingues, Ayse Demirkan, André G. Uitterlinden, Gerhard Liebisch, A. Cecile J.W. Janssens, Peter Ugocsai, Peter P. Pramstaller, Joshua C. Bis, Susan Campbell, Maksim Struchalin |
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| Přispěvatelé: | Epidemiology, Internal Medicine, Clinical Genetics, Groningen Biomolecular Sciences and Biotechnology, Bioinformatics, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Apolipoprotein E
Cancer Research Medicin och hälsovetenskap Epidemiology Medical and Health Sciences Biochemistry Carotid Intima-Media Thickness DISEASE chemistry.chemical_compound 0302 clinical medicine Delta-5 Fatty Acid Desaturase PHOSPHATIDYLCHOLINE Databases Genetic Phospholipids/blood CARDIoGRAM Consortium European Continental Ancestry Group/genetics Genetics (clinical) Phospholipids chemistry.chemical_classification 0303 health sciences Genome Sphingolipids/blood Single Nucleotide LYSOPHOSPHATIDYLCHOLINE Lipids HIGH-THROUGHPUT QUANTIFICATION 3. Good health Lysophosphatidylcholine Glycerophospholipid Fatty acid elongation Medicine lipids (amino acids peptides and proteins) FATTY-ACIDS Sphingomyelin Diabetes Mellitus Type 2/blood Human Research Article SUSCEPTIBILITY LOCI lcsh:QH426-470 Membrane lipids European Continental Ancestry Group Biology DIAGRAM Consortium Polymorphism Single Nucleotide White People HUMAN PLATELETS 03 medical and health sciences Databases SDG 3 - Good Health and Well-being Genetic Diabetes Mellitus Genetics Humans ddc:610 TANDEM MASS-SPECTROMETRY Polymorphism Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Type 2/blood 0604 Genetics Sphingolipids Population Biology Genome Human MEMBRANE-LIPIDS Fatty acid Human Genetics Sphingolipid lcsh:Genetics Metabolism chemistry ATHEROSCLEROSIS Diabetes Mellitus Type 2 Genetic Loci CHARGE Consortium 030217 neurology & neurosurgery EUROSPAN consortium Developmental Biology Genome-Wide Association Study |
| Zdroj: | PLoS Genetics PLoS Genetics, Vol 8, Iss 2, p e1002490 (2012) PLoS Genetics (print), 8(2). Public Library of Science Plos Genetics, 8(2). Public Library of Science PLoS genetics, 8(2):e1002490. PUBLIC LIBRARY SCIENCE Demirkan, A, van Duijn, C M, Ugocsai, P, Isaacs, A, Pramstaller, P P, Liebisch, G, Wilson, J F, Johansson, Å, Rudan, I, Aulchenko, Y S, Kirichenko, A V, Janssens, A C J W, Jansen, R C, Gnewuch, C, Domingues, F S, Pattaro, C, Wild, S H, Jonasson, I, Polasek, O, Zorkoltseva, I V, Hofman, A, Karssen, L C, Struchalin, M, Floyd, J, Igl, W, Biloglav, Z, Broer, L, Pfeufer, A, Pichler, I, Campbell, S, Zaboli, G, Kolcic, I, Rivadeneira, F, Huffman, J, Hastie, N D, Uitterlinden, A, Franke, L, Franklin, C S, Vitart, V, Nelson, C P, Preuss, M, Bis, J C, O'Donnell, C J, Franceschini, N, Witteman, J C M, Axenovich, T, Oostra, B A, Hayward, C & Wright, A F & Campbell, H 2012, ' Genome-wide association study identifies novel loci associated with circulating phospho-and sphingolipid concentrations ', PLoS Genetics, vol. 8, no. 2, pp. e1002490 . https://doi.org/10.1371/journal.pgen.1002490 PLoS Genetics; Vol 8 |
| ISSN: | 1553-7404 1553-7390 |
| DOI: | 10.1371/journal.pgen.1002490 |
| Popis: | 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 Author Summary Phospho- and sphingolipids are integral to membrane formation and are involved in crucial cellular functions such as signalling, membrane fluidity, membrane protein trafficking, neurotransmission, and receptor trafficking. In addition to severe monogenic diseases resulting from defective phospho- and sphingolipid function and metabolism, the evidence suggests that variations in these lipid levels at the population level are involved in the determination of cardiovascular and neurologic traits and subsequent disease. We took advantage of modern laboratory methods, including microarray-based genotyping and electrospray ionization tandem mass spectrometry, to hunt for genetic variation influencing the levels of more than 350 phospho- and sphingolipid phenotypes. We identified nine novel loci, in addition to confirming a number of previously described loci. Several other genetic regions provided substantial evidence of their involvement in these traits. All of these loci are strong candidates for further research in the field of lipid biology and are likely to yield considerable insights into the complex metabolic pathways underlying circulating phospho- and sphingolipid levels. Understanding these mechanisms might help to illuminate factors leading to the development of common cardiovascular and neurological diseases and might provide molecular targets for the development of new therapies. |
| Databáze: | OpenAIRE |
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