Association of the FTO obesity risk variant rs8050136 with percentage of energy intake from fat in multiple racial/ethnic populations

Sungshim Lani Park, Iona Cheng, Sarah A. Pendergrass, Anna M. Kucharska-Newton, Unhee Lim, Jose Luis Ambite, Christian P. Caberto, Kristine R. Monroe, Fredrick Schumacher, Lucia A. Hindorff, Matthew T. Oetjens, Sarah Wilson, Robert J. Goodloe, Shelly Ann Love, Brian E. Henderson, Laurence N. Kolonel, Christopher A. Haiman, Dana C. Crawford, Kari E. North, Gerardo HeissMarylyn D. Ritchie, Lynne R. Wilkens, Loïc Le Marchand

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 (βmeta = 0.2244 (standard error, 0.0548); P = 4 × 10 -5) and inversely associated with percentage of calories derived from carbohydrate (βmeta = -0.2796 (standard error, 0.0709); P = 8 × 10-5). 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.

Original languageEnglish (US)
Pages (from-to)780-790
Number of pages11
JournalAmerican journal of epidemiology
Volume178
Issue number5
DOIs
StatePublished - Sep 1 2013

All Science Journal Classification (ASJC) codes

  • Epidemiology

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