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Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups
Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by es...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858696/ https://www.ncbi.nlm.nih.gov/pubmed/20421936 http://dx.doi.org/10.1371/journal.pgen.1000916 |
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author | Scherag, André Dina, Christian Hinney, Anke Vatin, Vincent Scherag, Susann Vogel, Carla I. G. Müller, Timo D. Grallert, Harald Wichmann, H.-Erich Balkau, Beverley Heude, Barbara Jarvelin, Marjo-Riitta Hartikainen, Anna-Liisa Levy-Marchal, Claire Weill, Jacques Delplanque, Jérôme Körner, Antje Kiess, Wieland Kovacs, Peter Rayner, Nigel W. Prokopenko, Inga McCarthy, Mark I. Schäfer, Helmut Jarick, Ivonne Boeing, Heiner Fisher, Eva Reinehr, Thomas Heinrich, Joachim Rzehak, Peter Berdel, Dietrich Borte, Michael Biebermann, Heike Krude, Heiko Rosskopf, Dieter Rimmbach, Christian Rief, Winfried Fromme, Tobias Klingenspor, Martin Schürmann, Annette Schulz, Nadja Nöthen, Markus M. Mühleisen, Thomas W. Erbel, Raimund Jöckel, Karl-Heinz Moebus, Susanne Boes, Tanja Illig, Thomas Froguel, Philippe Hebebrand, Johannes Meyre, David |
author_facet | Scherag, André Dina, Christian Hinney, Anke Vatin, Vincent Scherag, Susann Vogel, Carla I. G. Müller, Timo D. Grallert, Harald Wichmann, H.-Erich Balkau, Beverley Heude, Barbara Jarvelin, Marjo-Riitta Hartikainen, Anna-Liisa Levy-Marchal, Claire Weill, Jacques Delplanque, Jérôme Körner, Antje Kiess, Wieland Kovacs, Peter Rayner, Nigel W. Prokopenko, Inga McCarthy, Mark I. Schäfer, Helmut Jarick, Ivonne Boeing, Heiner Fisher, Eva Reinehr, Thomas Heinrich, Joachim Rzehak, Peter Berdel, Dietrich Borte, Michael Biebermann, Heike Krude, Heiko Rosskopf, Dieter Rimmbach, Christian Rief, Winfried Fromme, Tobias Klingenspor, Martin Schürmann, Annette Schulz, Nadja Nöthen, Markus M. Mühleisen, Thomas W. Erbel, Raimund Jöckel, Karl-Heinz Moebus, Susanne Boes, Tanja Illig, Thomas Froguel, Philippe Hebebrand, Johannes Meyre, David |
author_sort | Scherag, André |
collection | PubMed |
description | Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10(−8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10(−7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults. |
format | Text |
id | pubmed-2858696 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28586962010-04-26 Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups Scherag, André Dina, Christian Hinney, Anke Vatin, Vincent Scherag, Susann Vogel, Carla I. G. Müller, Timo D. Grallert, Harald Wichmann, H.-Erich Balkau, Beverley Heude, Barbara Jarvelin, Marjo-Riitta Hartikainen, Anna-Liisa Levy-Marchal, Claire Weill, Jacques Delplanque, Jérôme Körner, Antje Kiess, Wieland Kovacs, Peter Rayner, Nigel W. Prokopenko, Inga McCarthy, Mark I. Schäfer, Helmut Jarick, Ivonne Boeing, Heiner Fisher, Eva Reinehr, Thomas Heinrich, Joachim Rzehak, Peter Berdel, Dietrich Borte, Michael Biebermann, Heike Krude, Heiko Rosskopf, Dieter Rimmbach, Christian Rief, Winfried Fromme, Tobias Klingenspor, Martin Schürmann, Annette Schulz, Nadja Nöthen, Markus M. Mühleisen, Thomas W. Erbel, Raimund Jöckel, Karl-Heinz Moebus, Susanne Boes, Tanja Illig, Thomas Froguel, Philippe Hebebrand, Johannes Meyre, David PLoS Genet Research Article Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10(−8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10(−7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults. Public Library of Science 2010-04-22 /pmc/articles/PMC2858696/ /pubmed/20421936 http://dx.doi.org/10.1371/journal.pgen.1000916 Text en Scherag et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Scherag, André Dina, Christian Hinney, Anke Vatin, Vincent Scherag, Susann Vogel, Carla I. G. Müller, Timo D. Grallert, Harald Wichmann, H.-Erich Balkau, Beverley Heude, Barbara Jarvelin, Marjo-Riitta Hartikainen, Anna-Liisa Levy-Marchal, Claire Weill, Jacques Delplanque, Jérôme Körner, Antje Kiess, Wieland Kovacs, Peter Rayner, Nigel W. Prokopenko, Inga McCarthy, Mark I. Schäfer, Helmut Jarick, Ivonne Boeing, Heiner Fisher, Eva Reinehr, Thomas Heinrich, Joachim Rzehak, Peter Berdel, Dietrich Borte, Michael Biebermann, Heike Krude, Heiko Rosskopf, Dieter Rimmbach, Christian Rief, Winfried Fromme, Tobias Klingenspor, Martin Schürmann, Annette Schulz, Nadja Nöthen, Markus M. Mühleisen, Thomas W. Erbel, Raimund Jöckel, Karl-Heinz Moebus, Susanne Boes, Tanja Illig, Thomas Froguel, Philippe Hebebrand, Johannes Meyre, David Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title | Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title_full | Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title_fullStr | Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title_full_unstemmed | Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title_short | Two New Loci for Body-Weight Regulation Identified in a Joint Analysis of Genome-Wide Association Studies for Early-Onset Extreme Obesity in French and German Study Groups |
title_sort | two new loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in french and german study groups |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858696/ https://www.ncbi.nlm.nih.gov/pubmed/20421936 http://dx.doi.org/10.1371/journal.pgen.1000916 |
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