title: Association between FTO variant and change in body weight and its interaction with dietary factors: the DiOGenes study.
abstract: Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (β (SE), 0.17 (0.08) kg·m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g·year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations.
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Lars
authors.initials: L
authors.lastname: Ängquist
authors.forename: Rikke D
authors.initials: RD
authors.lastname: Hansen
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.forename: Nabila
authors.initials: N
authors.lastname: Bouatia-Naji
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Marianne U
authors.initials: MU
authors.lastname: Jakobsen
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Karina
authors.initials: K
authors.lastname: Meidtner
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
mesh_terms: D000328:Adult; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D016022:Case-Control Studies; D004032:Diet; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D038321:Glycemic Index; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D055105:Waist Circumference / Q000235:genetics; D015430:Weight Gain / Q000235:genetics*
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human