title: Replication of the Association of BDNF and MC4R Variants With Dietary Intake in the Diabetes Prevention Program.
abstract: Genomewide association studies (GWAS) have identified consistent associations with obesity, with a number of studies implicating eating behavior as a primary mechanism. Few studies have replicated genetic associations with dietary intake. This study evaluates the association between obesity susceptibility loci and dietary intake.
  
  
  
  Data were obtained as part of the Diabetes Prevention Program (DPP), a clinical trial of diabetes prevention in persons at high risk of diabetes. The association of 31 genomewide association studies identified obesity risk alleles with dietary intake, measured through a food frequency questionnaire, was investigated in 3,180 participants from DPP at baseline.
  
  
  
  The minor allele at BDNF, identified as protective against obesity, was associated with lower total caloric intake (β = -106.06, SE = 33.13; p = .0014) at experimentwide statistical significance (p = .0016), whereas association of MC4R rs571312 with higher caloric intake reached nominal significance (β = 61.32, SE = 26.24; p = .0194). Among non-Hispanic white participants, the association of BDNF rs2030323 with total caloric intake was stronger (β = -151.99, SE = 30.09; p < .0001), and association of FTO rs1421085 with higher caloric intake (β = 56.72, SE = 20.69; p = .0061) and percentage fat intake (β = 0.37, SE = 0.08; p = .0418) was also observed.
  
  
  
  These results demonstrate with the strength of independent replication that BDNF rs2030323 is associated with 100 to 150 greater total caloric intake per allele, with additional contributions of MC4R and, in non-Hispanic white individuals, FTO. As it has been argued that an additional 100 kcal/d could account for the trends in weight gain, prevention focusing on genetic profiles with high dietary intake may help to quell adverse obesity trends.
  
  
  
  Clinicaltrials.gov,NCT00004992.
authors.affiliation: From the Weight Control and Diabetes Research Center (McCaffery, Wing), The Miriam Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI; The Biostatistics Center (Jablonski), The George Washington University, Rockville, MD; Genetic and Molecular Epidemiology Unit (Franks), Department of Clinical Sciences, Lund University, Malmo, Sweden; Department of Medicine, Umeå University, Umeå, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA; Massachusetts General Hospital Diabetes Center (Delahanty), Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Medstar Health Research Institute (Aroda), Hyattsville, MD; Indiana University (Marrero), Indianapolis, IN; Colorado School of Public Health, Department of Epidemiology (Hamman), University of Colorado Denver, Aurora, CO; Joslin Diabetes Center (Horton), Boston, MA; University of Tennessee (Dagogo-Jack), Memphis, TN; Department of Epidemiology and Population Health (Wylie-Rosett), Albert Einstein College of Medicine, Bronx, NY; University of California San Diego (Barrett-Connor), La Jolla, CA; University of Pittsburgh (Kitabchi), Pittsburgh, PA; Diabetes Epidemiology and Clinical Research Section (Knowler), National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ; and Diabetes Research Center (Diabetes Unit) and Center for Human Genetic Research (Florez), Massachusetts General Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: McCaffery
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: Linda M
authors.initials: LM
authors.lastname: Delahanty
authors.forename: Vanita
authors.initials: V
authors.lastname: Aroda
authors.forename: David
authors.initials: D
authors.lastname: Marrero
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hamman
authors.forename: Edward S
authors.initials: ES
authors.lastname: Horton
authors.forename: Samuel
authors.initials: S
authors.lastname: Dagogo-Jack
authors.forename: Judith
authors.initials: J
authors.lastname: Wylie-Rosett
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: Abbas
authors.initials: A
authors.lastname: Kitabchi
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Rena R
authors.initials: RR
authors.lastname: Wing
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D015992:Body Mass Index; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003920:Diabetes Mellitus / Q000517:prevention & control; D002149:Energy Intake / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human