Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
Détails
Télécharger: BIB_BAF4921EBDF5.P001.pdf (370.23 [Ko])
Etat: Public
Version: Final published version
Etat: Public
Version: Final published version
ID Serval
serval:BIB_BAF4921EBDF5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
Périodique
Plos Genetics
Collaborateur⸱rice⸱s
GIANT Consortium, MAGIC Consortium, GLGC Consortium
Contributeur⸱rice⸱s
Dupuis J., Langenberg C., Prokopenko I., Saxena R., Soranzo N., Jackson AU., Wheeler E., Glazer NL., Bouatia-Naji N., Gloyn AL., Lindgren CM., Mägi R., Morris AP., Randall J., Johnson T., Elliott P., Rybin D., Thorleifsson G., Steinthorsdottir V., Henneman P., Grallert H., Dehghan A., Hottenga JJ., Franklin CS., Navarro P., Song K., Goel A., Perry JR., Egan JM., Lajunen T., Grarup N., Sparsø T., Doney A., Voight BF., Stringham HM., Li M., Kanoni S., Shrader P., Cavalcanti-Proença C., Kumari M., Qi L., Timpson NJ., Gieger C., Zabena C., Rocheleau G., Ingelsson E., An P., O'Connell J., Luan£££Jian'an£££ J. , Elliott A., McCarroll SA., Payne F., Roccasecca RM., Pattou F., Sethupathy P., Ardlie K., Ariyurek Y., Balkau B., Barter P., Beilby JP., Ben-Shlomo Y., Benediktsson R., Bennett AJ., Bergmann S., Bochud M., Boerwinkle E., Bonnefond A., Bonnycastle LL., Borch-Johnsen K., Böttcher Y., Brunner E., Bumpstead SJ., Charpentier G., Chen YD., Chines P., Clarke R., Coin LJ., Cooper MN., Cornelis M., Crawford G., Crisponi L., Day IN., de Geus EJ. , Delplanque J., Dina C., Erdos MR., Fedson AC., Fischer-Rosinsky A., Forouhi NG., Fox CS., Frants R., Franzosi MG., Galan P., Goodarzi MO., Graessler J., Groves CJ., Grundy S., Gwilliam R., Gyllensten U., Hadjadj S., Hallmans G., Hammond N., Han X., Hartikainen AL., Hassanali N., Hayward C., Heath SC., Hercberg S., Herder C., Hicks AA., Hillman DR., Hingorani AD., Hofman A., Hui J., Hung J., Isomaa B., Johnson PR., Jørgensen T., Jula A., Kaakinen M., Kaprio J., Kesaniemi YA., Kivimaki M., Knight B., Koskinen S., Kovacs P., Kyvik KO., Lathrop GM., Lawlor DA., Le Bacquer O., Lecoeur C., Li Y., Lyssenko V., Mahley R., Mangino M., Manning AK., Martínez-Larrad£££María Teresa£££ MT. , McAteer JB., McCulloch LJ., McPherson R., Meisinger C., Melzer D., Meyre D., Mitchell BD., Morken MA., Mukherjee S., Naitza S., Narisu N., Neville MJ., Oostra BA., Orrù M., Pakyz R., Palmer CN., Paolisso G., Pattaro C., Pearson D., Peden JF., Pedersen NL., Perola M., Pfeiffer AF., Pichler I., Polasek O., Posthuma D., Potter SC., Pouta A., Province MA., Psaty BM., Rathmann W., Rayner NW., Rice K., Ripatti S., Rivadeneira F., Roden M., Rolandsson O., Sandbaek A., Sandhu M., Sanna S., Sayer AA., Scheet P., Scott LJ., Seedorf U., Sharp SJ., Shields B., Sigurðsson G., Sijbrands EJ., Silveira A., Simpson L., Singleton A., Smith NL., Sovio U., Swift A., Syddall H., Syvänen AC., Tanaka T., Thorand B., Tichet J., Tönjes A., Tuomi T., Uitterlinden AG., van Dijk KW. , van Hoek M., Varma D., Visvikis-Siest S., Vitart V., Vogelzangs N., Waeber G., Wagner PJ., Walley A., Walters GB., Ward KL., Watkins H., Weedon MN., Wild SH., Willemsen G., Witteman JC., Yarnell JW., Zeggini E., Zelenika D., Zethelius B., Zhai G., Zhao JH., Zillikens MC., Borecki IB., Loos RJ., Meneton P., Magnusson PK., Nathan DM., Williams GH., Hattersley AT., Silander K., Salomaa V., Smith GD., Bornstein SR., Schwarz P., Spranger J., Karpe F., Shuldiner AR., Cooper C., Dedoussis GV., Serrano-Ríos M., Morris AD., Lind L., Palmer LJ., Hu FB., Franks PW., Ebrahim S., Marmot M., Kao WH., Pankow JS., Sampson MJ., Kuusisto J., Laakso M., Hansen T., Pedersen O., Pramstaller PP., Wichmann HE., Illig T., Rudan I., Wright AF., Stumvoll M., Campbell H., Wilson JF., Hamsten A., Bergman RN., Buchanan TA., Collins FS., Mohlke KL., Tuomilehto J., Valle TT., Altshuler D., Rotter JI., Siscovick DS., Penninx BW., Boomsma ID., Deloukas P., Spector TD., Frayling TM., Ferrucci L., Kong A., Thorsteinsdottir U., Stefansson K., van Duijn CM. , Aulchenko YS., Cao A., Scuteri A., Schlessinger D., Uda M., Ruokonen A., Jarvelin MR., Waterworth DM., Vollenweider P., Peltonen L., Mooser V., Abecasis RG., Wareham NJ., Sladek R., Froguel P., Watanabe RM., Meigs JB., Groop L., Boehnke M., McCarthy MI., Florez JC., Barroso£££Inês£££ I.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
8
Numéro
5
Pages
e1002695
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Résumé
Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits.
Mots-clé
Adult, Aged, Body Mass Index, Cytokines/genetics, European Continental Ancestry Group, Female, Genome-Wide Association Study, HapMap Project, Humans, Intra-Abdominal Fat, Lysophospholipase/genetics, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Proteins/genetics, Sex Characteristics, Subcutaneous Fat, Abdominal
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/01/2013 10:58
Dernière modification de la notice
20/08/2019 15:28