Genetic studies of body mass index yield new insights for obesity biology.

Auteur(s) :
Männistö S., Jousilahti P., Forouhi NG., Wareham NJ., Zheng W., Vohl MC., Bochud M., Eriksson JG., Tremblay A., Lind L., Adair LS., Franks PW., Qi L., Uusitupa M., Perola M., Kaprio J., Berndt SI., Le Marchand L., Chanock SJ., Gong J., Schumacher FR., Peters U., Hofman A., Bergman RN., Raitakari OT., Boerwinkle E., Koskenvuo M., Cusi D., Franco OH., Kivimäki M., Wilkens LR., Locke AE., Kahali B., Justice AE., Pers TH., Day FR., Powell C., Vedantam S., Buchkovich ML., Yang J., Croteau-Chonka DC., Esko T., Fall T., Ferreira T., Gustafsson S., Kutalik Z., Luan J., Mägi R., Randall JC., Winkler TW., Wood AR., Workalemahu T., Faul JD., Smith JA., Hua Zhao J., Zhao W., Cheng YJ., Fehrmann R., Hedman ÅK., Karjalainen J., Schmidt EM., Absher D., Amin N., Anderson D., Beekman M., Bolton JL., Bragg-Gresham JL., Buyske S., Demirkan A., Deng G., Ehret GB., Feenstra B., Feitosa MF., Fischer K., Goel A., Jackson AU., Kanoni S., Kleber ME., Kristiansson K., Lim U., Lotay V., Mangino M., Mateo Leach I., Medina-Gomez C., Medland SE., Nalls MA., Palmer CD., Pasko D., Pechlivanis S., Peters MJ., Prokopenko I., Shungin D., Stancáková A., Strawbridge RJ., Ju Sung Y., Tanaka T., Teumer A., Trompet S., van der Laan SW., van Setten J., Van Vliet-Ostaptchouk JV., Wang Z., Yengo L., Zhang W., Isaacs A., Albrecht E., Ärnlöv J., Arscott GM., Attwood AP., Bandinelli S., Barrett A., Bas IN., Bellis C., Bennett AJ., Berne C., Blagieva R., Blüher M., Böhringer S., Bonnycastle LL., Böttcher Y., Boyd HA., Bruinenberg M., Caspersen IH., Ida Chen YD., Clarke R., Warwick Daw E., de Craen AJ., Delgado G., Dimitriou M., Doney AS., Eklund N., Estrada K., Eury E., Folkersen L., Fraser RM., Garcia ME., Geller F., Giedraitis V., Gigante B., Go AS., Golay A., Goodall AH., Gordon SD., Gorski M., Grabe HJ., Grallert H., Grammer TB., Gräßler J., Grönberg H., Groves CJ., Gusto G., Haessler J., Hall P., Haller T., Hallmans G., Hartman CA., Hassinen M., Hayward C., Heard-Costa NL., Helmer Q., Hengstenberg C., Holmen O., Hottenga JJ., James AL., Jeff JM., Johansson Å., Jolley J., Juliusdottir T., Kinnunen L., Koenig W., Kratzer W., Laitinen J., Lamina C., Leander K., Lee NR., Lichtner P., Lindström J., Sin Lo K., Lobbens S., Lorbeer R., Lu Y., Mach F., Magnusson PK., Mahajan A., McArdle WL., McLachlan S., Menni C., Merger S., Mihailov E., Milani L., Moayyeri A., Monda KL., Morken MA., Mulas A., Müller G., Müller-Nurasyid M., Musk AW., Nagaraja R., Nöthen MM., Nolte IM., Pilz S., Rayner NW., Renstrom F., Rettig R., Ried JS., Ripke S., Robertson NR., Rose LM., Sanna S., Scharnagl H., Scholtens S., Scott WR., Seufferlein T., Shi J., Vernon Smith A., Smolonska J., Stanton AV., Steinthorsdottir V., Stirrups K., Stringham HM., Sundström J., Swertz MA., Swift AJ., Syvänen AC., Tan ST., Tayo BO., Thorand B., Thorleifsson G., Tyrer JP., Uh HW., Vandenput L., Verhulst FC., Vermeulen SH., Verweij N., Vonk JM., Waite LL., Warren HR., Waterworth D., Weedon MN., Willenborg C., Wilsgaard T., Wojczynski MK., Wong A., Wright AF., Zhang Q., Brennan EP., Choi M., Dastani Z., Drong AW., Eriksson P., Franco-Cereceda A., Gådin JR., Gharavi AG., Goddard ME., Handsaker RE., Huang J., Karpe F., Kathiresan S., Keildson S., Kiryluk K., Kubo M., Lee JY., Liang L., Lifton RP., Ma B., McCarroll SA., McKnight AJ., Min JL., Moffatt MF., Montgomery GW., Murabito JM., Nicholson G., Nyholt DR., Okada Y., Perry JR., Dorajoo R., Reinmaa E., Salem RM., Sandholm N., Scott RA., Stolk L., Takahashi A., Tanaka T., Van't Hooft FM., Vinkhuyzen AA., Westra HJ., Zondervan KT., Heath AC., Arveiler D., Bakker SJ., Beilby J., Blangero J., Bovet P., Campbell H., Caulfield MJ., Cesana G., Chakravarti A., Chasman DI., Chines PS., Collins FS., Crawford DC., Adrienne Cupples L., Danesh J., de Faire U., den Ruijter HM., Dominiczak AF., Erbel R., Erdmann J., Farrall M., Felix SB., Ferrannini E., Ferrières J., Ford I., Forrester T., Gansevoort RT., Gejman PV., Gieger C., Gottesman O., Gudnason V., Gyllensten U., Hall AS., Harris TB., Hattersley AT., Hicks AA., Hindorff LA., Hingorani AD., Homuth G., Kees Hovingh G., Humphries SE., Hunt SC., Hyppönen E., Illig T., Jacobs KB., Jarvelin MR., Jöckel KH., Johansen B., Wouter Jukema J., Jula AM., Kastelein JJ., Keinanen-Kiukaanniemi SM., Kiemeney LA., Knekt P., Kooner JS., Kooperberg C., Kovacs P., Kraja AT., Kumari M., Kuusisto J., Lakka TA., Langenberg C., Lehtimäki T., Lyssenko V., Marette A., Matise TC., McKenzie CA., McKnight B., Moll FL., Morris AD., Morris AP., Murray JC., Nelis M., Ohlsson C., Oldehinkel AJ., Ong KK., Madden PA., Pasterkamp G., Peden JF., Petersen A., Postma DS., Pramstaller PP., Price JF., Rankinen T., Rao DC., Rice TK., Ridker PM., Rioux JD., Ritchie MD., Rudan I., Salomaa V., Samani NJ., Saramies J., Sarzynski MA., Schunkert H., Schwarz PE., Sever P., Shuldiner AR., Sinisalo J., Stolk RP., Strauch K., Tönjes A., Trégouët DA., Tremoli E., Virtamo J., Völker U., Waeber G., Willemsen G., Witteman JC., Zillikens MC., Amouyel P., Asselbergs FW., Assimes TL., Boehm BO., Bornstein SR., Bottinger EP., Bouchard C., Cauchi S., Chambers JC., Cooper RS., de Bakker PI., Dedoussis GV., Ferrucci L., Froguel P., Groop LC., Haiman CA., Hamsten A., Hui J., Hunter DJ., Hveem K., Kaplan RC., Kuh D., Laakso M., Liu Y., Martin NG., März W., Melbye M., Metspalu A., Moebus S., Munroe PB., Njølstad I., Oostra BA., Palmer CN., Pedersen NL., Pérusse L., Power C., Quertermous T., Rauramaa R., Rivadeneira F., Saaristo TE., Saleheen D., Sattar N., Schadt EE., Schlessinger D., Eline Slagboom P., Snieder H., Spector TD., Thorsteinsdottir U., Stumvoll M., Tuomilehto J., Uitterlinden AG., van der Harst P., Walker M., Wallaschofski H., Watkins H., Weir DR., Wichmann HE., Wilson JF., Zanen P., Borecki IB., Deloukas P., Fox CS., Heid IM., O'Connell JR., Strachan DP., Stefansson K., van Duijn CM., Abecasis GR., Franke L., Frayling TM., McCarthy MI., Visscher PM., Scherag A., Willer CJ., Boehnke M., Mohlke KL., Lindgren CM., Beckmann JS., Barroso I., North KE., Ingelsson E., Hirschhorn JN., Loos RJ., Speliotes EK.
Date :
Fév, 2015
Source(s) :
NATURE. #518:7538 p197-206
Adresse :
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.

Sommaire de l'article

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Source : Pubmed
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