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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
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نویسنده
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scherag a. ,dina c. ,hinney a. ,vatin v. ,scherag s. ,vogel c.i.g. ,müller t.d. ,grallert h. ,wichmann h.-e. ,balkau b. ,heude b. ,jarvelin m.-r. ,hartikainen a.-l. ,levy-marchal c. ,weill j. ,delplanque j. ,körner a. ,kiess w. ,kovacs p. ,rayner n.w. ,prokopenko i. ,mccarthy m.i. ,schäfer h. ,jarick i. ,boeing h. ,fisher e. ,reinehr t. ,heinrich j. ,rzehak p. ,berdel d. ,borte m. ,biebermann h. ,krude h. ,rosskopf d. ,rimmbach c. ,rief w. ,fromme t. ,klingenspor m. ,schürmann a. ,schulz n. ,nöthen m.m. ,mühleisen t.w. ,erbel r. ,jöckel k.-h. ,moebus s. ,boes t. ,illig t. ,froguel p. ,hebebrand j. ,meyre d.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 4
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چکیده
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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 populationbased 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. © 2010 scherag et al.
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آدرس
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institute for medical informatics,biometry and epidemiology,university of duisburg-essen,essen,germany,department of child and adolescent psychiatry,university of duisburg-essen,essen, Germany, centre national de la recherche scientifique (cnrs) 8090-institute of biology,pasteur institute,lille, France, department of child and adolescent psychiatry,university of duisburg-essen,essen, Germany, centre national de la recherche scientifique (cnrs) 8090-institute of biology,pasteur institute,lille, France, department of child and adolescent psychiatry,university of duisburg-essen,essen, Germany, department of child and adolescent psychiatry,university of duisburg-essen,essen, Germany, department of child and adolescent psychiatry,university of duisburg-essen,essen,germany,department of psychiatry,university of cincinnati genome research institute,cincinnati,oh, United States, helmholtz zentrum münchen,german research center for environmental health,institute of epidemiology,munich-neuherberg, Germany, helmholtz zentrum münchen,german research center for environmental health,institute of epidemiology,munich-neuherberg,germany,institute of medical data management,biometrics,and epidemiology,ludwig-maximilians university munich,munich, Germany, inserm,cesp centre for research in epidemiology and population health,u1018,epidemiology of diabetes,obesity and chronic kidney disease over the lifecourse,université paris sud 11,umrs 1018,villejuif, France, inserm,cesp centre for research in epidemiology and population health,u1018,epidemiology of diabetes,obesity and chronic kidney disease over the lifecourse,université paris sud 11,umrs 1018,villejuif, France, department of epidemiology and public health,imperial college london,london,united kingdom,institute of health sciences,department of child and adolescent health,national public health institute,biocenter oulu,university of oulu,oulu, Finland, department of clinical sciences/obstetrics and gynecology,university of oulu,oulu, Finland, inserm,u690,université paris diderot,paris, France, pediatric endocrine unit,jeanne de flandre hospital,lille, France, centre national de la recherche scientifique (cnrs) 8090-institute of biology,pasteur institute,lille, France, university hospital for children and adolescents,university of leipzig,leipzig, Germany, university hospital for children and adolescents,university of leipzig,leipzig, Germany, department of internal medicine iii,interdisciplinary centre for clinical research,university of leipzig,leipzig, Germany, oxford centre for diabetes,endocrinology and metabolism,university of oxford,churchill hospital,oxford,united kingdom,the wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, oxford centre for diabetes,endocrinology and metabolism,university of oxford,churchill hospital,oxford,united kingdom,the wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, oxford centre for diabetes,endocrinology and metabolism,university of oxford,churchill hospital,oxford,united kingdom,the wellcome trust centre for human genetics,university of oxford,oxford, United Kingdom, institute of medical biometry and epidemiology,philipps-university of marburg,marburg, Germany, institute of medical biometry and epidemiology,philipps-university of marburg,marburg, Germany, department of epidemiology,german institute of human nutrition potsdam-rehbrücke,nuthetal, Germany, department of epidemiology,german institute of human nutrition potsdam-rehbrücke,nuthetal, Germany, institute for paediatric nutrition medicine,vestische hospital for children and adolescents,university of witten/herdecke,datteln, Germany, helmholtz zentrum münchen,german research center for environmental health,institute of epidemiology,munich-neuherberg,germany,institute of medical data management,biometrics,and epidemiology,ludwig-maximilians university munich,munich, Germany, helmholtz zentrum münchen,german research center for environmental health,institute of epidemiology,munich-neuherberg,germany,institute of medical data management,biometrics,and epidemiology,ludwig-maximilians university munich,munich, Germany, department of paediatrics,marien-hospital wesel,wesel, Germany, children's hospital,municipal hospital 'st georg',leipzig,germany,department of pediatrics,university of leipzig,leipzig, Germany, institute of experimental pediatric endocrinology,charité-universitätsmedizin berlin,berlin, Germany, institute of experimental pediatric endocrinology,charité-universitätsmedizin berlin,berlin, Germany, institute for pharmacology,ernst-moritz-arndt university,greifswald, Germany, institute for pharmacology,ernst-moritz-arndt university,greifswald, Germany, department of clinical psychology and psychotherapy,faculty of psychology,university of marburg, Germany, molecular nutritional medicine,technische universität münchen,else kröner-fresenius center,freising-weihenstephan, Germany, molecular nutritional medicine,technische universität münchen,else kröner-fresenius center,freising-weihenstephan, Germany, department of pharmacology,german institute of human nutrition potsdam-rehbruecke,nuthetal, Germany, department of pharmacology,german institute of human nutrition potsdam-rehbruecke,nuthetal, Germany, institute of human genetics,university of bonn,bonn,germany,department of genomics,life and brain center,university of bonn,bonn, Germany, institute of human genetics,university of bonn,bonn,germany,department of genomics,life and brain center,university of bonn,bonn, Germany, department of cardiology,university of duisburg-essen,essen, Germany, institute for medical informatics,biometry and epidemiology,university of duisburg-essen,essen, Germany, institute for medical informatics,biometry and epidemiology,university of duisburg-essen,essen, Germany, institute for medical informatics,biometry and epidemiology,university of duisburg-essen,essen, Germany, helmholtz zentrum münchen,german research center for environmental health,institute of epidemiology,munich-neuherberg,germany,institute of medical data management,biometrics,and epidemiology,ludwig-maximilians university munich,munich, Germany, centre national de la recherche scientifique (cnrs) 8090-institute of biology,pasteur institute,lille,france,department of genomic medicine,imperial college london,hammersmith hospital,london, United Kingdom, department of child and adolescent psychiatry,university of duisburg-essen,essen, Germany, centre national de la recherche scientifique (cnrs) 8090-institute of biology,pasteur institute,lille, France
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Authors
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