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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.
PLoS Genet 2010; 6(4):e1000916PG

Abstract

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 = 1.85x10(-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 = 4.84x10(-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 approximately 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.

Authors+Show Affiliations

Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany. andre.scherag@uk-essen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20421936

Citation

Scherag, André, et al. "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." PLoS Genetics, vol. 6, no. 4, 2010, pp. e1000916.
Scherag A, Dina C, Hinney A, et al. 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. PLoS Genet. 2010;6(4):e1000916.
Scherag, A., Dina, C., Hinney, A., Vatin, V., Scherag, S., Vogel, C. I., ... Meyre, D. (2010). 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. PLoS Genetics, 6(4), pp. e1000916. doi:10.1371/journal.pgen.1000916.
Scherag A, et al. 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. PLoS Genet. 2010 Apr 22;6(4):e1000916. PubMed PMID: 20421936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Scherag,André, AU - Dina,Christian, AU - Hinney,Anke, AU - Vatin,Vincent, AU - Scherag,Susann, AU - Vogel,Carla I G, AU - Müller,Timo D, AU - Grallert,Harald, AU - Wichmann,H-Erich, AU - Balkau,Beverley, AU - Heude,Barbara, AU - Jarvelin,Marjo-Riitta, AU - Hartikainen,Anna-Liisa, AU - Levy-Marchal,Claire, AU - Weill,Jacques, AU - Delplanque,Jérôme, AU - Körner,Antje, AU - Kiess,Wieland, AU - Kovacs,Peter, AU - Rayner,Nigel W, AU - Prokopenko,Inga, AU - McCarthy,Mark I, AU - Schäfer,Helmut, AU - Jarick,Ivonne, AU - Boeing,Heiner, AU - Fisher,Eva, AU - Reinehr,Thomas, AU - Heinrich,Joachim, AU - Rzehak,Peter, AU - Berdel,Dietrich, AU - Borte,Michael, AU - Biebermann,Heike, AU - Krude,Heiko, AU - Rosskopf,Dieter, AU - Rimmbach,Christian, AU - Rief,Winfried, AU - Fromme,Tobias, AU - Klingenspor,Martin, AU - Schürmann,Annette, AU - Schulz,Nadja, AU - Nöthen,Markus M, AU - Mühleisen,Thomas W, AU - Erbel,Raimund, AU - Jöckel,Karl-Heinz, AU - Moebus,Susanne, AU - Boes,Tanja, AU - Illig,Thomas, AU - Froguel,Philippe, AU - Hebebrand,Johannes, AU - Meyre,David, Y1 - 2010/04/22/ PY - 2009/09/18/received PY - 2010/03/19/accepted PY - 2010/4/28/entrez PY - 2010/4/28/pubmed PY - 2010/8/11/medline SP - e1000916 EP - e1000916 JF - PLoS genetics JO - PLoS Genet. VL - 6 IS - 4 N2 - 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 = 1.85x10(-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 = 4.84x10(-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 approximately 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/20421936/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_ L2 - http://dx.plos.org/10.1371/journal.pgen.1000916 DB - PRIME DP - Unbound Medicine ER -