Meta-Analysis

. 2016 Sep 20:354:i4707.

doi: 10.1136/bmj.i4707.

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

Katherine M Livingstone¹, Carlos Celis-Morales², George D Papandonatos³, Bahar Erar³, Jose C Florez⁴, Kathleen A Jablonski⁵, Cristina Razquin⁶, Amelia Marti⁷, Yoriko Heianza⁸, Tao Huang⁹, Frank M Sacks¹⁰, Mathilde Svendstrup¹¹, Xuemei Sui¹², Timothy S Church¹³, Tiina Jääskeläinen¹⁴, Jaana Lindström¹⁵, Jaakko Tuomilehto¹⁶, Matti Uusitupa¹⁷, Tuomo Rankinen¹⁸, Wim H M Saris¹⁹, Torben Hansen²⁰, Oluf Pedersen²⁰, Arne Astrup²¹, Thorkild I A Sørensen²², Lu Qi²³, George A Bray¹³, Miguel A Martinez-Gonzalez⁷, J Alfredo Martinez²⁴, Paul W Franks²⁵, Jeanne M McCaffery²⁶, Jose Lara²⁷, John C Mathers²⁸

Affiliations

¹ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Deakin University, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Victoria, Australia.
² Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK.
³ Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
⁴ Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁵ George Washington University Department of Epidemiology and Biostatistics The Biostatistics Center, Rockville, MD, USA.
⁶ Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain.
⁷ CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
⁸ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
⁹ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
¹⁰ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark.
¹² Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
¹³ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
¹⁴ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Department of Medical and Clinical Genetics, University of Helsinki, Finland.
¹⁵ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹⁶ Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁷ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
¹⁸ Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
¹⁹ Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Maastricht, Netherlands.
²⁰ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²¹ Department of Nutrition, Exercise and Sports, Copenhagen University, Rolighedsvej 30, Frederiksberg C, Denmark.
²² Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Denmark.
²³ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁴ CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain Food Science and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
²⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
²⁶ The Miriam Hospital and the Alpert School of Medicine, Brown University, Providence, USA.
²⁷ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
²⁸ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK john.mathers@newcastle.ac.uk.

PMID: 27650503
PMCID: PMC6168036
DOI: 10.1136/bmj.i4707

Meta-Analysis

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

Katherine M Livingstone et al. BMJ. 2016.

. 2016 Sep 20:354:i4707.

doi: 10.1136/bmj.i4707.

Authors

Affiliations

¹ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Deakin University, Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Victoria, Australia.
² Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK.
³ Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
⁴ Diabetes Unit and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA Programs in Metabolism and Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
⁵ George Washington University Department of Epidemiology and Biostatistics The Biostatistics Center, Rockville, MD, USA.
⁶ Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain.
⁷ CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain.
⁸ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA.
⁹ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Epidemiology Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
¹⁰ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹¹ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Diabetes Academy, Odense, Denmark.
¹² Department of Exercise Science, University of South Carolina, Columbia, SC, USA.
¹³ Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
¹⁴ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland Department of Medical and Clinical Genetics, University of Helsinki, Finland.
¹⁵ Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
¹⁶ Dasman Diabetes Institute, Dasman, Kuwait City, Kuwait Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁷ Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
¹⁸ Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
¹⁹ Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre +, Maastricht, Netherlands.
²⁰ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²¹ Department of Nutrition, Exercise and Sports, Copenhagen University, Rolighedsvej 30, Frederiksberg C, Denmark.
²² Novo Nordisk Foundation Centre for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Denmark.
²³ Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
²⁴ CIBER Fisiopatologia de la Obesidad y Nutricion and PREDIMED Network from Instituto de Salud Carlos III Spanish Government, Spain Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Spain Food Science and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
²⁵ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
²⁶ The Miriam Hospital and the Alpert School of Medicine, Brown University, Providence, USA.
²⁷ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK Department of Applied Sciences, Faculty of Health and Life Sciences, Northumbria University, Newcastle upon Tyne, UK.
²⁸ Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, UK john.mathers@newcastle.ac.uk.

PMID: 27650503
PMCID: PMC6168036
DOI: 10.1136/bmj.i4707

Erratum in

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials.
[No authors listed] [No authors listed] BMJ. 2017 Jan 17;356:j263. doi: 10.1136/bmj.j263. BMJ. 2017. PMID: 28096080 Free PMC article. No abstract available.

Abstract

Objective: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.

Design: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.

Data sources: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.

Eligibility criteria for study selection: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.

Results: We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.

Conclusions: We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.

Systematic review registration: PROSPERO CRD42015015969.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from companies for the submitted work; no relationships with companies that might have an interest in the submitted work in the previous three years; no spouses, partners, or children have no financial relationships that may be relevant to the submitted work; no non-financial interests that may be relevant to the submitted work.

Figures

None — **Fig 1** Study selection flow diagram based on preferred reporting items for systematic reviews and meta-analyses statement

See this image and copyright information in PMC

Comment in

Obesity treatment-are personalised approaches missing the point?
Tedstone AE. Tedstone AE. BMJ. 2016 Sep 20;354:i4980. doi: 10.1136/bmj.i4980. BMJ. 2016. PMID: 27650604 No abstract available.

References

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1. Willyard C. Heritability: The family roots of obesity. Nature 2014;508:S58-6010.1038/508S58a. - PubMed

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FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

Affiliations

FTO genotype and weight loss: systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials

Authors

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Erratum in

Abstract

Conflict of interest statement

Figures

Comment in

References

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Medical