Pleiotropic genes for metabolic syndrome and inflammation
| العنوان: | Pleiotropic genes for metabolic syndrome and inflammation |
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| المؤلفون: | Inga Prokopenko, Fasil Tekola-Ayele, Jerome I. Rotter, Audrey Y. Chu, Torben Jørgensen, Paul M. Ridker, Yan V. Sun, Daniel I. Chasman, M. Arfan Ikram, Marit E. Jørgensen, Ruth J. F. Loos, Zari Dastani, Martin G. Larson, Andrew D. Johnson, Jennifer A. Smith, Ahmad Vaez, Albert Hofman, Letizia Marullo, Ilja M. Nolte, Abbas Dehghan, Michael A. Province, Leslie A. Lange, Josef Coresh, Christopher J. O'Donnell, Aldi T. Kraja, Eric Boerwinkle, Torben Hansen, Josée Dupuis, Honghuang Lin, Mary F. Feitosa, Renate B. Schnabel, Emelia J. Benjamin, Sarah A. Pendergrass, Weihong Tang, Ingrid B. Borecki, Yaming Shao, W. H. Linda Kao, Alanna C. Morrison, Alexander P. Reiner, Russell P. Tracy, Diane M. Becker, Yi-Hsiang Hsu, Benjamin F. Voight, Dhananjay Vaidya, James S. Pankow, Tuomas O. Kilpeläinen, Kari E. North, Oscar H. Franco, Lisa R. Yanek, Marylyn D. Ritchie, Sharon L.R. Kardia, Rebecca Rohde, James G. Wilson, Mike A. Nalls, Laura J. Rasmussen-Torvik, James B. Meigs, Symen Ligthart, Harold Snieder, Behrooz Z. Alizadeh, Andrew P. Morris, Charles N. Rotimi, Oluf Pedersen, Ronald P. Stolk, Mark Ziegler, André G. Uitterlinden, J. Brent Richards, Santhi K. Ganesh, Hae Kyung Im |
| المساهمون: | Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Epidemiology, Public Health, Internal Medicine, Radiology & Nuclear Medicine |
| المصدر: | Molecular Genetics and Metabolism, 112(4), 317-338. ACADEMIC PRESS INC ELSEVIER SCIENCE Molecular Genetics and Metabolism, 112(4), 317-338. Academic Press |
| بيانات النشر: | Academic Press, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Endocrinology, Diabetes and Metabolism, NF-KAPPA-B, Inflammatory markers, Women's Genome Health Study, Genome-wide association study, BLOOD-PRESSURE, Research & Experimental Medicine, Bioinformatics, Biochemistry, Endocrinology, Cohorts for Heart and, Pleiotropy, Genetic Investigation of Anthropometric Traits Consortium, Gene Regulatory Networks, Meta-Analyses of Glucose, Genetics, Genetics & Heredity, Pleiotropic associations, INSULIN-RESISTANCE, Metabolic Syndrome X, Genetic Pleiotropy, Global Lipids Genetics Consortium, Insulin-related traits Consortium, Metabolic syndrome, C-REACTIVE PROTEIN, Phenotype, Medicine, Research & Experimental, DENSITY-LIPOPROTEIN CHOLESTEROL, CARDIOVASCULAR-DISEASE, CORONARY-ARTERY-DISEASE, CIRCULATING ADIPONECTIN, ADIPOGen Consortium, Life Sciences & Biomedicine, Aging Research in Genetic Epidemiology, Howard University Family Study, Single-nucleotide polymorphism, Quantitative trait locus, Biology, Article, Endocrinology & Metabolism, Quantitative Trait, Heritable, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, medicine, SNP, Humans, Cross Consortia Pleiotropy Group, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Molecular Biology, Global BPgen Consortium, Inflammation, Science & Technology, Computational Biology, Regulome, 1103 Clinical Sciences, medicine.disease, Genetic architecture, DIABETES SUSCEPTIBILITY LOCI, Meta-analysis, Biomarkers, Genome-Wide Association Study |
| الوصف: | Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation. (C) 2014 Elsevier Inc. All rights reserved. |
| وصف الملف: | application/pdf |
| تدمد: | 1096-7206 1096-7192 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ab131ee4b502c7d5d6c68e50d80d528Test https://doi.org/10.1016/j.ymgme.2014.04.007Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0ab131ee4b502c7d5d6c68e50d80d528 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10967206 10967192 |
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