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  • Original Article
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FTO predicts weight regain in the Look AHEAD clinical trial

International Journal of Obesity volume 37, pages 1545–1552 (2013)Cite this article

Subjects

Abstract

Background:

Genome-wide association studies have provided new insights into the genetic factors that contribute to the development of obesity. We hypothesized that these genetic markers would also predict magnitude of weight loss and weight regain after initial weight loss.

Methods:

Established obesity risk alleles available on the Illumina CARe iSelect (IBC) chip were characterized in 3899 overweight or obese participants with type 2 diabetes from the Look AHEAD (Action for Health in Diabetes), a randomized trial to determine the effects of intensive lifestyle intervention (ILI) and diabetes support and education (DSE) on cardiovascular morbidity and mortality. Primary analyses examined the interaction between 13 obesity risk polymorphisms in eight genes and randomized treatment arm in predicting weight change at year 1, and weight regain at year 4 among individuals who lost 3% or more of their baseline weight by year 1.

Results:

No single-nucleotide polymorphisms (SNPs) were significantly associated with magnitude of weight loss or interacted with treatment arm at year 1. However, fat mass and obesity associated gene (FTO) rs3751812 predicted weight regain within DSE (1.56 kg per risk allele, P=0.005), but not ILI (P=0.761), resulting in SNP × treatment arm interaction (P=0.009). In a partial replication of prior research, the obesity risk (G) allele at BDNF rs6265 was associated with greater weight regain across treatment arms (0.773 kg per risk allele), although results were of borderline statistical significance (P=0.051).

Conclusions:

Variations in the FTO and BDNF loci may contribute risk of weight regain after weight loss.

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Acknowledgements

We acknowledge the Look AHEAD sites that participated in this ancillary study. This study is supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135 and DK56992. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women’s Health; and the Centers for Disease Control and Prevention. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center (M01RR01066); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (M01RR000056 44) and NIH grants (DK 046204 and DK072497); and VA Puget Sound Health Care System and Department of Veterans Affairs; Frederic C Bartter General Clinical Research Center (M01RR01346). AKH was supported by the Training Program in Cardiovascular Research (NIH, 5T32HL069770). The following organizations have committed to make major contributions to Look AHEAD: Federal Express; Health Management Resources; Johnson & Johnson, LifeScan Inc.; Optifast-Novartis Nutrition; Roche Pharmaceuticals; Ross Product Division of Abbott Laboratories; Slim-Fast Foods Company; and Unilever.

Author information

Author notes

  1. See Appendix.

Authors and Affiliations

  1. Department of Psychiatry and Human Behavior, Weight Control and Diabetes Research Center, The Miriam Hospital and Brown Medical School, Providence, RI, USA

    J M McCaffery & R R Wing

  2. Center of Statistical Sciences, Brown University, Providence, RI, USA

    G D Papandonatos

  3. MCRI Center for Translational Genomics, Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA, USA

    G S Huggins

  4. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA

    I Peter

  5. Division of Metabolism, Department of Medicine, Endocrinology and Nutrition, University of Washington, VA Puget Sound Health Care System, Seattle, WA, USA

    S E Kahn & A E Kitabchi

  6. National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA

    W C Knowler

  7. Baylor College of Medicine and Michael E DeBakey VA Medical Center, Houston, TX, USA

    G E Hudnall

  8. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee Health Science Center, Memphis, TN, USA

    E W Lipkin

  9. Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA

    L E Wagenknecht

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Consortia

The Genetic Subgroup of Look AHEAD

The Look AHEAD Research Group

Corresponding author

Correspondence to J M McCaffery.

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Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

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Appendix

Appendix

Johns Hopkins Medical Institutions: Frederick L Brancati, MD, MHS1; Jeff Honas, MS2; Lawrence Cheskin, MD3; Jeanne M Clark, MD, MPH3; Kerry Stewart, EdD3; Richard Rubin, PhD3; Jeanne Charleston, RN; Kathy Horak, RD.

Pennington Biomedical Research Center: George A Bray, MD1; Kristi Rau2; Allison Strate, RN2; Brandi Armand, LPN2; Frank L Greenway, MD3; Donna H Ryan, MD3; Donald Williamson, PhD3; Amy Bachand; Michelle Begnaud; Betsy Berhard; Elizabeth Caderette; Barbara Cerniauskas; David Creel; Diane Crow; Helen Guay; Nancy Kora; Kelly LaFleur; Kim Landry; Missy Lingle; Jennifer Perault; Mandy Shipp, RD; Marisa Smith; Elizabeth Tucker.

University of Alabama at Birmingham: Cora E Lewis, MD, MSPH1; Sheikilya Thomas MPH2; Monika Safford, MD3; Vicki DiLillo, PhD; Charlotte Bragg, MS, RD, LD; Amy Dobelstein; Stacey Gilbert, MPH; Stephen Glasser, MD; Sara Hannum, MA; Anne Hubbell, MS; Jennifer Jones, MA; DeLavallade Lee; Ruth Luketic, MA, MBA, MPH; Karen Marshall; L Christie Oden; Janet Raines, MS; Cathy Roche, RN, BSN; Janet Truman; Nita Webb, MA; Audrey Wrenn, MAEd.

Harvard Center

Massachusetts General Hospital: David M Nathan, MD1; Heather Turgeon, RN, BS, CDE2; Kristina Schumann, BA2; Enrico Cagliero, MD3; Linda Delahanty, MS, RD3; Kathryn Hayward, MD3; Ellen Anderson, MS, RD3; Laurie Bissett, MS, RD; Richard Ginsburg, PhD; Valerie Goldman, MS, RD; Virginia Harlan, MSW; Charles McKitrick, RN, BSN, CDE; Alan McNamara, BS; Theresa Michel, DPT, DSc CCS; Alexi Poulos, BA; Barbara Steiner, EdM; Joclyn Tosch, BA.

Joslin Diabetes Center: Edward S Horton, MD1; Sharon D Jackson, MS, RD, CDE2; Osama Hamdy, MD, PhD3; A Enrique Caballero, MD3; Sarah Bain, BS; Elizabeth Bovaird, BSN, RN; Ann Goebel-Fabbri, PhD; Lori Lambert, MS, RD; Sarah Ledbury, MEd, RD; Maureen Malloy, BS; Kerry Ovalle, MS, RCEP, CDE.

Beth Israel Deaconess Medical Center: George Blackburn, MD, PhD1; Christos Mantzoros, MD, DSc3; Kristinia Day, RD; Ann McNamara, RN.

University of Colorado Health Sciences Center: James O Hill, PhD1; Marsha Miller, MS, RD2; JoAnn Phillipp, MS2; Robert Schwartz, MD3; Brent Van Dorsten, PhD3; Judith Regensteiner, PhD3; Salma Benchekroun MS; Ligia Coelho, BS; Paulette Cohrs, RN, BSN; Elizabeth Daeninck, MS, RD; Amy Fields, MPH; Susan Green; April Hamilton, BS, CCRC; Jere Hamilton, BA; Eugene Leshchinskiy; Michael McDermott, MD; Lindsey Munkwitz, BS; Loretta Rome, TRS; Kristin Wallace, MPH; Terra Worley, BA.

Baylor College of Medicine: John P Foreyt, PhD1; Rebecca S Reeves, DrPH, RD2; Henry Pownall, PhD3; Ashok Balasubramanyam, MBBS3; Peter Jones, MD3; Michele Burrington, RD; Chu-Huang Chen, MD, PhD; Allyson Clark, RD; Molly Gee, MEd, RD; Sharon Griggs; Michelle Hamilton; Veronica Holley; Jayne Joseph, RD; Patricia Pace, RD: Julieta Palencia, RN; Olga Satterwhite, RD; Jennifer Schmidt; Devin Volding, LMSW; Carolyn White.

University of Tennessee Health Science Center

University of Tennessee East: Karen C Johnson, MD, MPH1; Carolyn Gresham, RN2; Stephanie Connelly, MD, MPH3; Amy Brewer, RD, MS; Mace Coday, PhD; Lisa Jones, RN; Lynne Lichtermann, RN, BSN; Shirley Vosburg, RD, MPH; and J Lee Taylor, MEd, MBA.

University of Tennessee Downtown: Abbas E Kitabchi, PhD, MD1; Helen Lambeth, RN, BSN2; Debra Clark, LPN; Andrea Crisler, MT; Gracie Cunningham; Donna Green, RN; Debra Force, MS, RD, LDN; Robert Kores, PhD; Renate Rosenthal PhD; Elizabeth Smith, MS, RD, LDN; and Maria Sun, MS, RD, LDN; and Judith Soberman, MD3.

University of Minnesota: Robert W Jeffery, PhD1; Carolyn Thorson, CCRP2; John P Bantle, MD3; J Bruce Redmon, MD3; Richard S Crow, MD3; Scott Crow, MD3; Susan K Raatz, PhD, RD3; Kerrin Brelje, MPH, RD; Carolyne Campbell; Jeanne Carls, MEd; Tara Carmean-Mihm, BA; Emily Finch, MA; Anna Fox, MA; Elizabeth Hoelscher, MPH, RD, CHES; La Donna James; Vicki A Maddy, BS, RD; Therese Ockenden, RN; Birgitta I Rice, MS, RPh CHES; Tricia Skarphol, BS; Ann D Tucker, BA; Mary Susan Voeller, BA; Cara Walcheck, BS, RD.

St Luke’s Roosevelt Hospital Center: Xavier Pi-Sunyer, MD1; Jennifer Patricio, MS2; Stanley Heshka, PhD3; Carmen Pal, MD3; Lynn Allen, MD; Diane Hirsch, RNC, MS, CDE; Mary Anne Holowaty, MS, CN.

University of Pennsylvania: Thomas A Wadden, PhD1; Barbara J Maschak-Carey, MSN, CDE2; Stanley Schwartz, MD3; Gary D Foster, PhD3; Robert I Berkowitz, MD3; Henry Glick, PhD3; Shiriki K Kumanyika, PhD, RD, MPH3; Johanna Brock; Helen Chomentowski; Vicki Clark; Canice Crerand, PhD; Renee Davenport; Andrea Diamond, MS, RD; Anthony Fabricatore, PhD; Louise Hesson, MSN; Stephanie Krauthamer-Ewing, MPH; Robert Kuehnel, PhD; Patricia Lipschutz, MSN; Monica Mullen, MS, RD; Leslie Womble, PhD, MS; Nayyar Iqbal, MD.

University of Pittsburgh: David E Kelley, MD1; Jacqueline Wesche-Thobaben, RN, BSN, CDE2; Lewis Kuller, MD, DrPH3; Andrea Kriska, PhD3; Janet Bonk, RN, MPH; Rebecca Danchenko, BS; Daniel Edmundowicz, MD3; Mary L Klem, PhD, MLIS3; Monica E Yamamoto, DrPH, RD, FADA 3; Barb Elnyczky, MA; George A Grove, MS; Pat Harper, MS, RD, LDN; Janet Krulia, RN, BSN, CDE; Juliet Mancino, MS, RD, CDE, LDN; Anne Mathews, MS, RD, LDN; Tracey Y Murray, BS; Joan R Ritchea; Jennifer Rush, MPH; Karen Vujevich, RN-BC, MSN, CRNP; Donna Wolf, MS.

Miriam Hospital/Brown Medical School: Rena R Wing, PhD1; Renee Bright, MS2; Vincent Pera, MD3; John Jakicic, PhD3; Deborah Tate, PhD3; Amy Gorin, PhD3; Kara Gallagher, PhD3; Amy Bach, PhD; Barbara Bancroft, RN, MS; Anna Bertorelli, MBA, RD; Richard Carey, BS; Tatum Charron, BS; Heather Chenot, MS; Kimberley Chula-Maguire, MS; Pamela Coward, MS, RD; Lisa Cronkite, BS; Julie Currin, MD; Maureen Daly, RN; Caitlin Egan, MS; Erica Ferguson, BS, RD; Linda Foss, MPH; Jennifer Gauvin, BS; Don Kieffer, PhD; Lauren Lessard, BS; Deborah Maier, MS; JP Massaro, BS; Tammy Monk, MS; Rob Nicholson, PhD; Erin Patterson, BS; Suzanne Phelan, PhD; Hollie Raynor, PhD, RD; Douglas Raynor, PhD; Natalie Robinson, MS, RD; Deborah Robles; Jane Tavares, BS.

University of Texas Health Science Center at San Antonio: Steven M Haffner, MD1; Maria G Montez, RN, MSHP, CDE2; Carlos Lorenzo, MD3.

University of Washington/VA Puget Sound Health Care System: Steven Kahn MB, ChB1; Brenda Montgomery, RN, MS, CDE2; Robert Knopp, MD3; Edward Lipkin, MD3; Matthew L Maciejewski, PhD3; Dace Trence, MD3; Terry Barrett, BS; Joli Bartell, BA; Diane Greenberg, PhD; Anne Murillo, BS; Betty Ann Richmond, MEd; April Thomas, MPH, RD.

Coordinating Center, Wake Forest University: Mark A Espeland, PhD1; Judy L Bahnson, BA2; Lynne Wagenknecht, DrPH3; David Reboussin, PhD3; W Jack Rejeski, PhD3; Alain Bertoni, MD, MPH3; Wei Lang, PhD3; Gary Miller, PhD3; David Lefkowitz, MD3; Patrick S Reynolds, MD3; Paul Ribisl, PhD3; Mara Vitolins, DrPH3; Michael Booth, MBA2; Kathy M Dotson, BA2; Amelia Hodges, BS2; Carrie C Williams, BS2; Jerry M Barnes, MA; Patricia A Feeney, MS; Jason Griffin, BS; Lea Harvin, BS; William Herman, MD, MPH; Patricia Hogan, MS; Sarah Jaramillo, MS; Mark King, BS; Kathy Lane, BS; Rebecca Neiberg, MS; Andrea Ruggiero, MS; Christian Speas, BS; Michael P Walkup, MS; Karen Wall, AAS; Michelle Ward; Delia S West, PhD; Terri Windham.

Central Laboratory, Northwest Lipid Research Laboratories: Santica M Marcovina, PhD, ScD1; Greg Strylewicz, MS.

Federal Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases: Barbara Harrison, MS; Van S Hubbard, MD PhD; Susan ZYanovski, MD.

National Heart, Lung, and Blood Institute: Lawton S Cooper, MD, MPH; Jeffrey Cutler, MD, MPH; Eva Obarzanek, PhD, MPH, RD.

Centers for Disease Control and Prevention: Edward W Gregg, PhD; David F Williamson, PhD; Ping Zhang, PhD.

1 Principal Investigator

2 Program Coordinator

3 Co-Investigator

All other Look AHEAD staffs are listed alphabetically by site.

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McCaffery, J., Papandonatos, G., Huggins, G. et al. FTO predicts weight regain in the Look AHEAD clinical trial. Int J Obes 37, 1545–1552 (2013). https://doi.org/10.1038/ijo.2013.54

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