July 10, 2013
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PAGE Study: Genetic link to obesity depends on dietary intake

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Genome-wide association studies have found common genetic variants associated with BMI. However, obesity risk variants associated with macronutrient intake have not been validated, according to Sungshim Lani Park, MS, PhD, of the epidemiology program at the University of Hawaii Cancer Center, and colleagues.

“To further understand the relationship between obesity single-nucleotide polymorphisms (SNPs) and energy consumption, we investigated, as part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, the relationship between six obesity risk variants and intake of macronutrients (carbohydrate, protein, ethanol, and fat and its subtypes) among type 2 diabetes-free adults from five racial/ethnic groups,” Park and colleagues wrote.

Sungshim Lani Park, MS, PhD 

Sungshim Lani Park

According to researchers, they assessed obesity risk variants in or near the NEGR1, TMEM18, BDNF, FTO, MC4R and KCTD15 genes and macronutrient intake (i.e., carbohydrate, protein, ethanol, and fat) in 3 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 used patient data from the National Health and Nutrition Examination Survey (NHANES, 1991-1994; n=6,347).

After adjustments, a fixed analysis model indicated that the FTO rs8050136 A allele (n=36,973) was positively linked to a percentage of calories obtained from fat (beta-meta=0.2244; standard error=0.0548); P=4×10−5) and inversely related to a percentage of calories obtained from carbohydrates (beta-meta=−0.2796; standard error=0.0709; P=8×10−5), according to data.

Further, percentage of calories from fat measured at baseline was discovered to be a partial mediator of the rs8050136 effect on BMI measured at follow-up (variability=0.0823 kg/m2; 95% CI, 0.0559-0.1128), according to data from the multiethnic cohort study.

These data demonstrate that risk variant associations on or near the FTO gene are partially due to dietary intake, they wrote.

Disclosure: The researchers report no relevant financial disclosures.