Exome-derived adiponectin-associated variants implicate obesity and lipid biology
| العنوان: | Exome-derived adiponectin-associated variants implicate obesity and lipid biology |
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| المؤلفون: | Peter Kovacs, Judith B. Borja, Karen L. Mohlke, Jennifer Kriebel, Kent D. Taylor, Stuart MacGregor, Ruth J. F. Loos, Carol A. Wang, Cornelia M. van Duijn, Samuli Ripatti, Ko Willems van Dijk, Jaeyoung Hong, Yingchang Lu, Leslie A. Lange, Terho Lehtimäki, Matthias Blüher, Cassandra N. Spracklen, Michael A. Province, Craig E. Pennell, Laura B. L. Wittemans, Yii-Der Ida Chen, Alex P. Reiner, Nicholas J. Wareham, Massimo Mangino, Kristin L. Young, Tuomas O. Kilpeläinen, David A. Mackey, Michael Preuss, Mika Kähönen, Sara M. Willems, Paraskevi Chirstofidou, Tamara B. Harris, Matthew A. Allison, Michael Boehnke, Jian'an Luan, Cristina Venturini, Kari E. North, Chelsea K. Raulerson, Linda Broer, Paul M. Ridker, Colleen M. Sitlani, Xiuqing Guo, Leo-Pekka Lyytikäinen, Neil Roberston, Pekka Jousilahti, Barbara McKnight, M. Arfan Ikram, Heather M. Highland, Torben Hansen, Niels Grarup, Satu Männistö, James G. Wilson, Konstantin Strauch, Mariaelisa Graff, Ayse Demirkan, Rebecca S. Fine, Tugce Karaderi, Linda S. Adair, Jie Yao, Olli T. Raitakari, Zoltán Kutalik, Jeffrey Haesser, Veikko Salomaa, Sophie Molnos, Rebecca D. Jackson, Renée de Mutsert, Markku Laakso, Mark I. McCarthy, Carolina Medina-Gomez, America A. Sandoval-Zárate, Anke Tönjes, Daniel I. Chasman, Shuai Wang, Michael Stumvoll, Jette Bork-Jensen, Claudia Langenberg, Paul L. Auer, Anubha Mahajan, Claudia Schurmann, Mary F. Feitosa, Melissa E. Garcia, Tim D. Spector, Aruna D. Pradhan, Jorge R. Kizer, Timothy M. Frayling, Ying Wu, James B. Meigs, Andrew P. Morris, Harald Grallert, André G. Uitterlinden, Cecilia M. Lindgren, Traci M. Bartz, Mike A. Nalls, Erik Ingelsson, Jerome I. Rotter, Mark Walker, Ruifang Li-Gao, Ivana Nedeljkovic, Najaf Amin, Hanieh Yaghootkar, Dennis O. Mook-Kanamori, Betina H. Thuesen, Lars Lind, Jin Li |
| المساهمون: | Epidemiology, Internal Medicine, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Samuli Olli Ripatti / Principal Investigator, University Management, Biostatistics Helsinki, University of Helsinki, Institute for Molecular Medicine Finland, Complex Disease Genetics, Medical and Clinical Psychology |
| المصدر: | Am. J. Hum. Genet. 105, 15-28 (2019) American Journal of Human Genetics, 105(1), 15-28. CELL PRESS Spracklen, C N, Karaderi, T, Yaghootkar, H, Schurmann, C, Fine, R S, Kutalik, Z, Preuss, M H, Lu, Y, Wittemans, L B L, Adair, L S, Allison, M, Amin, N, Auer, P L, Bartz, T M, Blüher, M, Boehnke, M, Borja, J B, Bork-Jensen, J, Broer, L, Chasman, D I, Chen, Y-D I, Chirstofidou, P, Demirkan, A, van Duijn, C M, Feitosa, M F, Garcia, M E, Graff, M, Grallert, H, Grarup, N, Guo, X, Haesser, J, Hansen, T, Harris, T B, Highland, H M, Hong, J, Ikram, M A, Ingelsson, E, Jackson, R, Jousilahti, P, Kähönen, M, Kizer, J R, Kovacs, P, Kriebel, J, Laakso, M, Lange, L A, Lehtimäki, T, Li, J, Li-Gao, R, Lind, L, Luan, J, Lyytikäinen, L-P, MacGregor, S, Mackey, D A, Mahajan, A, Mangino, M, Männistö, S, McCarthy, M I, McKnight, B, Medina-Gomez, C, Meigs, J B, Molnos, S, Mook-Kanamori, D, Morris, A P, de Mutsert, R, Nalls, M A, Nedeljkovic, I, North, K E, Pennell, C E, Pradhan, A D, Province, M A, Raitakari, O T, Raulerson, C K, Reiner, A P, Ridker, P M, Ripatti, S, Roberston, N, Rotter, J I, Salomaa, V, Sandoval-Zárate, A A, Sitlani, C M, Spector, T D, Strauch, K, Stumvoll, M, Taylor, K D, Thuesen, B, Tönjes, A, Uitterlinden, A G, Venturini, C, Walker, M, Wang, C A, Wang, S, Wareham, N J, Willems, S M, Willems van Dijk, K, Wilson, J G, Wu, Y, Yao, J, Young, K L, Langenberg, C, Frayling, T M, Kilpeläinen, T O, Lindgren, C M, Loos, R J F & Mohlke, K L 2019, ' Exome-Derived Adiponectin-Associated Variants Implicate Obesity and Lipid Biology ', American Journal of Human Genetics, vol. 105, no. 1, pp. 15-28 . https://doi.org/10.1016/j.ajhg.2019.05.002Test American Journal of Human Genetics, 105(1), 15-28. Cell Press |
| بيانات النشر: | Cell Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Candidate gene, Adipose tissue, Genome-wide association study, DISEASE, CANDIDATE GENES, 0302 clinical medicine, Cqardio metabolic traits, RARE, Exome, Genetics (clinical), Aged, 80 and over, Genetics, 0303 health sciences, 1184 Genetics, developmental biology, physiology, Hispanic or Latino, Middle Aged, Lipids, Phenotype, ADIPOSE-TISSUE, Adipose Tissue, 030220 oncology & carcinogenesis, Medical genetics, Female, CIRCULATING ADIPONECTIN, Adiponectin, Adult, EXPRESSION, medicine.medical_specialty, Adolescent, Quantitative Trait Loci, 030209 endocrinology & metabolism, Biology, Polymorphism, Single Nucleotide, Article, White People, Young Adult, 03 medical and health sciences, Cardio Metabolic Traits, Genome-wide Association Study, Obesity, SDG 3 - Good Health and Well-being, medicine, GLYCEMIC TRAITS, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Gene, METAANALYSIS, 030304 developmental biology, Aged, PLASMA ADIPONECTIN, Correction, medicine.disease, Human genetics, Black or African American, 030104 developmental biology, Expression quantitative trait loci, 3111 Biomedicine |
| الوصف: | Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p -7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p -4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels. |
| وصف الملف: | application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| اللغة: | English |
| تدمد: | 0002-9297 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4fd6ed1bd78dcedf46c844ef1cc0a15cTest https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=56283Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4fd6ed1bd78dcedf46c844ef1cc0a15c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00029297 |
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