SynthesisObesity reviews : an official journal of the International Association for the Study of Obesity2015
Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Obesity reviews : an official journal of the International Association for the Study of Obesity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3citing papers in PubMed
1.2field-weighted citation impact, top 17% of its field
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Who cites it
3 citing papers in PubMed, 8 citations in OpenAlex.
- The association between BMI and mortality using early adulthood BMI as an instrumental variable for midlife BMI.Scientific reports · 2018Article
- A Mathematical Model for Predicting Obesity Transmission with Both Genetic and Nongenetic Heredity.Obesity (Silver Spring, Md.) · 2018Article
- IsOncotarget · 2017Article
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Authors and funding
60 authors at 20 institutions in 18 countries.
E Zimmermann *Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark.
L H Ängquist *Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark.
S S MirzaDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
J H ZhaoMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
D I ChasmanDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
K FischerEstonian Genome Center, University of Tartu, Tartu, Estonia.
Q QiDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, New York, USA.
A V SmithIcelandic Heart Association, Kopavogur, Iceland.
M ThinggaardThe Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
M N JarczokMannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
M A NallsLaboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.
S TrompetDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
N J TimpsonMRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
B SchmidtInstitute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany.
A U JacksonDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
L P LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
N VerweijDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M Mueller-NurasyidDepartment of Medicine I, Ludwig-Maximilians-University, Munich, Germany.
M VikströmKarolinska Institutet, Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Stockholm, Sweden.
P Marques-VidalDepartment of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
A WongMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
K MeidtnerDepartment of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
R P MiddelbergQIMR Berghofer Medical Research Institute, Brisbane, Australia.
R J StrawbridgeAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
L ChristiansenThe Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
FTO-Mortality Collaborating Group
K O KyvikInstitute of Regional Health Services Research and Odense Patient data Explorative Network, Odense University Hospital, Odense, Denmark.
A HamstenAtherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
T JääskeläinenInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
A TjønnelandDanish Cancer Society Research Centre, Copenhagen, Denmark.
J G ErikssonDiabetes Prevention Unit, Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
J B WhitfieldQIMR Berghofer Medical Research Institute, Brisbane, Australia.
H BoeingDepartment of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
R HardyMRC Unit for Lifelong Health and Ageing, University College London, London, UK.
P VollenweiderDepartment of Internal Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
K LeanderKarolinska Institutet, Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, Stockholm, Sweden.
A PetersDeutsches Forschungszentrum für Herz-Kreislauferkrankungen (DZHK), Partner site Munich Heart Alliance, Munich, Germany.
P van der HarstDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M KumariDepartment of Epidemiology and Public Health, University College London, London, UK.
T LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
A MeirhaegheInserm, U744, Institut Pasteur de Lille, University Lille Nord de France, Lille, France.
J TuomilehtoDiabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
K-H JöckelInstitute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany.
Y Ben-ShlomoSchool of Social and Community Medicine, University of Bristol, Bristol, UK.
N SattarBHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, Glasgow, UK.
S E BaumeisterInstitute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
G Davey SmithMRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
J P CasasDepartment of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
D K HoustonDepartment of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston Salem, North Carolina, USA.
W MärzVth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
K ChristensenThe Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
V GudnasonIcelandic Heart Association, Kopavogur, Iceland.
F B HuDepartment of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
A MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia.
P M RidkerDivision of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
N J WarehamMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
R J F LoosMRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.
H TiemeierDepartment of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.
E SonestedtDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
T I A SørensenInstitute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark.
University of Bristol · GBBrigham and Women's Hospital · USKarolinska Institutet · SEMRC Unit for Lifelong Health and Ageing · GBChild Health and Development Institute · USFrederiksberg Hospital · DKHarvard University · USOdense University Hospital · DKQIMR Berghofer Medical Research Institute · AUUniversität für Weiterbildung Krems · ATUniversitätsmedizin Greifswald · DEUniversity Hospital of Lausanne · CHUniversity Medical Center Groningen · NLUniversity of Eastern Finland · FIUniversity of Essex · GBUniversity of Helsinki · FIUniversity of Iceland · ISUniversity of Southern Denmark · DKAlbert Einstein College of Medicine · USErasmus University Rotterdam · NL
Funding
Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8MValidity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI SPIEGELMAN, DONNA L · 1991 to 2009
$41.8MWomen's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2MTransgenic CoreP30DK046200 · NIDDK · TUFTS MEDICAL CENTER · PI HU, FRANK B · 1992 to 2021
$25.0MMolecular pathological epidemiology of colorectal cancerU01CA137088 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETERS, ULRIKE · 2009 to 2018
$21.8MRISK FACTORS FOR CVD IN WOMENR01HL034594 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI JoAnn Elisabeth Manson, Lu Qi · 1985 to 2026
$13.8MIdentifying Genes for Type 2 Diabetes: FUSIONU01DK062370 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BOEHNKE, MICHAEL L, SCOTT, LAURA J. · 2009 to 2021
$11.6MBIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HANKINSON, SUSAN E · 1989 to 2008
$11.3MRisk Factors for Ischemic Stroke in WomenR01HL088521 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REXRODE, KATHRYN M · 2008 to 2025
$9.9MSleep Duration, Childhood Energy Balance, and Insulin Resistance in AdolescenceU54CA155626 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI STAMPFER, MEIR · 2011 to 2015
$9.6MThe Pathobiology of NephrolithiasisP01DK070756 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI CURHAN, GARY C. · 2007 to 2011
$8.4MGene-Environment Interactions in GlaucomaR01EY015473 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI PASQUALE, LOUIS ROBERT · 2005 to 2021
$8.3MBritish Heart Foundation PG/13/66/30442British Heart Foundation RG/13/2/30098Cancer Research UK 14136Medical Research Council G0401527Medical Research Council G1000143Medical Research Council MC_U106179471Medical Research Council MC_UU_12013/1Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12019/1Medical Research Council MR/K013351/1Medical Research Council MR/L023784/2NCI NIH HHS CA055075NCI NIH HHS CA134958NCI NIH HHS CA49449NCI NIH HHS CA87969NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA047988NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA134958NCI NIH HHS U01 CA049449NCI NIH HHS U01 CA137088NCI NIH HHS U01CA137088NCI NIH HHS U54 CA155626NCI NIH HHS U54CA155626NCI NIH HHS UM1 CA182913NEI NIH HHS EY015473NEI NIH HHS R01 EY015473NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004399NHGRI NIH HHS U01HG004399NHGRI NIH HHS U01 HG004728NHGRI NIH HHS U01HG004728NHLBI NIH HHS HL071981NHLBI NIH HHS HL073168NHLBI NIH HHS HL088521NHLBI NIH HHS HL34594NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL036310NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL071981NHLBI NIH HHS R01 HL073168NHLBI NIH HHS R01 HL080467NHLBI NIH HHS R01 HL088521NIAAA NIH HHS R01 AA007535NIAAA NIH HHS R01 AA010249NIAAA NIH HHS R01 AA014041NIA NIH HHS N01 AG062101NIA NIH HHS N01 AG062103NIA NIH HHS N01 AG062106NIA NIH HHS R01 AG013196NIA NIH HHS R01 AG032098NIA NIH HHS R37 AG013196NIDDK NIH HHS DK08014NIDDK NIH HHS DK091718NIDDK NIH HHS DK098311NIDDK NIH HHS DK46200NIDDK NIH HHS DK58845NIDDK NIH HHS DK70756NIDDK NIH HHS K24 DK080140NIDDK NIH HHS K24 DK098311NIDDK NIH HHS P01 DK070756NIDDK NIH HHS P30 DK046200NIDDK NIH HHS P30DK46200NIDDK NIH HHS R01 DK058845NIDDK NIH HHS R01 DK062370NIDDK NIH HHS R01 DK091718NIDDK NIH HHS R56 DK062370NIDDK NIH HHS U01 DK062370NLM NIH HHS R01 LM010098Wellcome Trust
Abstract
Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.
Indexed as
Polymorphism, Single NucleotideAdiposityAlpha-Ketoglutarate-Dependent Dioxygenase FTOBody Mass IndexGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansObesityObservational Studies as TopicProteinsWaist CircumferenceAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, humanProteinsFTOmeta-analysismortalityobesity
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