Journal article
Genetic studies of body mass index yield new insights for obesity biology
Nature (London), Vol.518(7538), pp.197-206
02/12/2015
DOI: 10.1038/nature14177
PMCID: PMC4382211
PMID: 25673413
Abstract
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 upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 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 similar to 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 systemin 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.
Details
- Title: Subtitle
- Genetic studies of body mass index yield new insights for obesity biology
- Creators
- Adam E. Locke - University of MichiganBratati Kahali - University of MichiganSonja I. Berndt - National Cancer InstituteAnne E. Justice - University of North Carolina at Chapel HillTune H. Pers - Boston Children's HospitalFelix R. Day - MRC Epidemiology UnitCorey Powell - University of MichiganSailaja Vedantam - Boston Children's HospitalMartin L. Buchkovich - University of North Carolina at Chapel HillJian Yang - The University of QueenslandDamien C. Croteau-Chonka - University of North Carolina at Chapel HillTonu Esko - Boston Children's HospitalTove Fall - Karolinska InstitutetTeresa Ferreira - Centre for Human GeneticsStefan Gustafsson - Science for Life LaboratoryZoltan Kutalik - Institute of Social and Preventive MedicineJian'an Luan - University of CambridgeReedik Maegi - University of TartuJoshua C. Randall - Centre for Human GeneticsThomas W. Winkler - University of RegensburgAndrew R. Wood - University of ExeterTsegaselassie Workalemahu - Harvard UniversityJessica D. Faul - University of MichiganJennifer A. Smith - University of MichiganJing Hua Zhao - University of CambridgeWei Zhao - University of MichiganJin Chen - University of MichiganRudolf Fehrmann - University of GroningenÅsa K Hedman - Science for Life LaboratoryJuha Karjalainen - University Medical Center GroningenEllen M. Schmidt - University of MichiganDevin Absher - HudsonAlpha Institute for BiotechnologyNajaf Amin - Erasmus MCDenise Anderson - The University of Western AustraliaMarian Beekman - Leiden University Medical CenterJennifer L. Bolton - University of EdinburghL. Bragg-Gresham - University of MichiganSteven Buyske - Rutgers, The State University of New JerseyAyse Demirkan - Erasmus MCGuohong Deng - Army Medical UniversityGeorg B. Ehret - University Hospital of GenevaBjarke Feenstra - Statens Serum InstitutMary F. Feitosa - Washington University in St. LouisKrista Fischer - University of TartuAnuj Goel - Centre for Human GeneticsJian Gong - Fred Hutch Cancer CenterAnne U. Jackson - University of MichiganStavroula Kanoni - Queen Mary University of LondonMarcus E. Kleber - Heidelberg UniversityKati Kristiansson - Finnish Institute for Health and WelfareUnhee Lim - University of Hawaii Cancer CenterVaneet Lotay - Icahn School of Medicine at Mount SinaiMassimo Mangino - King's College LondonIrene Mateo Leach - University Medical Center GroningenCarolina Medina-Gomez - Erasmus MCSarah E. Medland - QIMR Berghofer Medical Research InstituteMichael A. Nalls - National Institute on AgingCameron D. Palmer - Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USADorota Pasko - University of ExeterSonali Pechlivanis - Institut für Medizinische Informatik, Biometrie und EpidemiologieMarjolein J. Peters - Erasmus MCInga Prokopenko - Centre for Human GeneticsDmitry Shungin - Lund UniversityAlena Stancakova - University of Eastern FinlandRona J. Strawbridge - Karolinska InstitutetYun Ju Sung - Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USAToshiko Tanaka - National Institute on AgingAlexander Teumer - Universitätsmedizin GreifswaldStella Trompet - Leiden University Medical CenterSander W. van der Laan - University Medical Center UtrechtJessica van Settee - Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 CX Utrecht, NetherlandsJana V. Van Vliet-Ostaptchouk - University Medical Center GroningenZhaoming Wang - NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USALoic Yengo - Centre National de la Recherche ScientifiqueWeihua Zhang - Ealing HospitalAaron Isaacs - Erasmus MCEva Albrecht - Helmholtz Zentrum MünchenJohan Arnlov - Uppsala UniversityGillian M. Arscott - Pathwest Laboratory MedicineAntony P. Attwood - NHS Blood and TransplantStefania Bandinelli - Azienda Sanitaria di FirenzeAmy Barrett - Oxford Centre for Diabetes, Endocrinology and MetabolismIsabelita N. Bas - University of San CarlosClaire Bellis - Texas Biomedical Research InstituteAmanda J. Bennett - Oxford Centre for Diabetes, Endocrinology and MetabolismChristian Berne - Uppsala UniversityRoza Blagieva - Universität UlmMatthias Blueher - Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, D-04103 Leipzig, GermanyStefan Bohringer - Leiden University Medical CenterLori L. Bonnycastle - National Human Genome Research InstituteYvonne Boettcher - Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, D-04103 Leipzig, GermanyHeather A. Boyd - Statens Serum InstitutMarcel Bruinenberg - University Medical Center GroningenIda H Caspersen - Norwegian University of Science and TechnologyYii-Der Ida Chen - Univ Calif Los Angeles, Dept Pediat, Torrance, CA 90502 USARobert Clarke - University of OxfordE. Warwick Daw - Washington University in St. LouisAnton J. M. de Craen - Leiden University Medical CenterGraciela Delgado - University Hospital HeidelbergMaria Dimitriou - Harokopio University of AthensADIPOGen ConsortiumJeffrey C Murray (Contributor)
- Resource Type
- Journal article
- Publication Details
- Nature (London), Vol.518(7538), pp.197-206
- DOI
- 10.1038/nature14177
- PMID
- 25673413
- PMCID
- PMC4382211
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4687
- Publisher
- NATURE PORTFOLIO
- Number of pages
- 23
- Grant note
- RG/07/008/23674; FS/14/55/30806; RG/10/12/28456; RG/08/014/24067; RG/08/008/25291 / British Heart Foundation NF-SI-0611-10099; NF-SI-0512-10114; NF-SI-0507-10380; NF-SI-0513-10109; NF-SI-0513-10059; NF-SI-0611-10219; NF-SI-0514-10027; NF-SI-0512-10113; NF-SI-0611-10170; NF-SI-0512-10165 / National Institute for Health Research; National Institutes of Health Research (NIHR) ES/J023299/1; ES/F02679X/1 / ESRC; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) CZB/4/672; CZB/4/710 / Chief Scientist Office; Chief Scientist Office - Scotland ES/F02679X/1; ES/J023299/1 / Economic and Social Research Council; UK Research & Innovation (UKRI); Economic & Social Research Council (ESRC) NNF13OC0005785; NNF14OC0010513; NNF15OC0016416; NNF13OC0004839; NNF14OC0009883; NNF12OC1016467 / Novo Nordisk Fonden; Novo Nordisk Foundation MC_UU_12019/1; MC_PC_U127561128; G1000143; MR/K006584/1; G0902037; MC_UU_12012/1; MC_UU_12015/2; G1000616; G0601261; MC_UU_12015/1; G19/35; G0600717; MC_UU_12012/5/B; G0600717B; G0100222; MC_UU_12015/5; MC_U106179472; MR/K013351/1; G9521010; MC_UU_12013/4; G1001799; MC_U106179471; MR/N01104X/1; MC_UP_A100_1003; MR/K002414/1; MC_UU_12013/1; MR/L003120/1; G0401527; G8802774 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Kilpeläinen Group; Pers Group / NNF Center for Basic Metabolic Research MC_U106179472; MC_UU_12015/5; G0600717; G0601261; MC_UU_12015/1; MC_UU_12012/1; G0902037; MC_UU_12019/1; MC_UU_12015/2; MR/K002414/1; MC_PC_U127561128; MC_UU_12013/1; MR/K013351/1; MC_UP_A100_1003; MR/L003120/1; G1001799; G9521010; G1000616; MR/N01104X/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 14136 / Cancer Research UK
- Language
- English
- Date published
- 02/12/2015
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985034987402771
Metrics
5 Record Views