Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
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
_version_ 1782180436012695552
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
work_keys_str_mv AT scheragandre twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT dinachristian twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT hinneyanke twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT vatinvincent twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT scheragsusann twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT vogelcarlaig twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT mullertimod twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT grallertharald twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT wichmannherich twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT balkaubeverley twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT heudebarbara twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT jarvelinmarjoriitta twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT hartikainenannaliisa twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT levymarchalclaire twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT weilljacques twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT delplanquejerome twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT kornerantje twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT kiesswieland twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT kovacspeter twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT raynernigelw twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT prokopenkoinga twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT mccarthymarki twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT schaferhelmut twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT jarickivonne twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT boeingheiner twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT fishereva twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT reinehrthomas twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT heinrichjoachim twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT rzehakpeter twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT berdeldietrich twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT bortemichael twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT biebermannheike twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT krudeheiko twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT rosskopfdieter twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT rimmbachchristian twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT riefwinfried twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT frommetobias twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT klingenspormartin twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT schurmannannette twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT schulznadja twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT nothenmarkusm twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT muhleisenthomasw twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT erbelraimund twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT jockelkarlheinz twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT moebussusanne twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT boestanja twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT illigthomas twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT froguelphilippe twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT hebebrandjohannes twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups
AT meyredavid twonewlociforbodyweightregulationidentifiedinajointanalysisofgenomewideassociationstudiesforearlyonsetextremeobesityinfrenchandgermanstudygroups