Novel locus including FGF21 is associated with dietary macronutrient intake

Abstract

Dietary intake of macronutrients (carbohydrate, protein, and fat) has been associated with risk of chronic conditions such as obesity and diabetes. Family studies have reported a moderate contribution of genetics to variation in macronutrient intake. In a genome-wide meta-analysis of a population-based discovery cohort (n = 33 533), rs838133 in FGF21 (19q13.33), rs197273 near TRAF family member-associated NF-kappa-B activator (TANK) (2p24.2), and rs10163409 in FTO (16q12.2) were among the top associations (P < 10(-5)) for percentage of total caloric intake from protein and carbohydrate. rs838133 was replicated in silico in an independent sample from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) Nutrition Working Group (n = 38 360) and attained genome-wide significance in combined analysis (Pjoint = 7.9 × 10(-9)). A cytokine involved in cellular metabolism, FGF21 is a potential susceptibility gene for obesity and type 2 diabetes. Our results highlight the potential of genetic variation for determining dietary macronutrient intake.

Figure 1.

Regional association plots showing −log10 P-values for percentage of total energy intake from macronutrients. Closest genes and -log10 P-values for SNPs at (A) chromosome 2q24, (B) chromosome16q12 and (C) chromosome 19q13 in association with percentage of total energy intake from carbohydrate (circles), protein (triangles) and fat (crosses) adjusted for BMI in the discovery cohort. The P-values from joint meta-analysis of DietGen and CHARGE Nutrition are indicated for association between (A) rs197273 and carbohydrate intake by the bolded circle and (C) rs838133 and protein intake by the bolded triangle. The threshold for genome-wide significance (P < 5 × 10⁻⁸) is indicated by the horizontal dotted line.