Résumé :
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[BDSP. Notice produite par INIST-CNRS A8spR0x8. Diffusion soumise à autorisation]. Common obesity risk variants have been associated with macronutrient intake ; however, these associations'generalizability across populations has not been demonstrated. We investigated the associations between 6 obesity risk variants in (or near) the NEGR1, TMEM18, BDNF, FTO, MC4R, and KCTD15 genes and macronutrient intake (carbohydrate, protein, ethanol, and fat) in 3 Population Architecture using Genomics and Epidemiology (PAGE) studies : the Multiethnic Cohort Study (1993-2006) (n=19,529), the Atherosclerosis Risk in Communities Study (1987-1989) (n=11,114), and the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) Study, which accesses data from the Third National Health and Nutrition Examination Survey (1991-1994) (n=6,347). We used linear regression, with adjustment for age, sex, and ethnicity, to estimate the associations between obesity risk genotypes and macronutrient intake. A fixed-effects meta-analysis model showed that the FTO rs8050136 A allele (n=36,973) was positively associated with percentage of calories derived from fat (bêtameta=0.2244 (standard error, 0.0548) ; P=4 x 10-5) and inversely associated with percentage of calories derived from carbohydrate (bêtameta=-0.2796 (standard error, 0.0709) ; P=8x10-5). In the Multiethnic Cohort Study, percentage of calories from fat assessed at baseline was a partial mediator of the rs8050136 effect on body mass index (weight (kg)/height (m) 2) obtained at 10 years of follow-up (mediation of effect=0.0823 kg/m2,95% confidence interval : 0.0559,0.1128). Our data provide additional evidence that the association of FTO with obesity is partially mediated by dietary intake.
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