Novel locus including FGF21 is associated with dietary macronutrient intake

• Published in: Human molecular genetics Vol. 22; no. 9; pp. 1895 - 1902
• Main Authors: Chu, Audrey Y., Workalemahu, Tsegaselassie, Paynter, Nina P., Rose, Lynda M., Giulianini, Franco, Tanaka, Toshiko, Ngwa, Julius S., Qi, Qibin, Curhan, Gary C., Rimm, Eric B., Hunter, David J., Pasquale, Louis R., Ridker, Paul M., Hu, Frank B., Chasman, Daniel I., Qi, Lu
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2013
• Subjects: Association Studies; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2 - genetics; Dietary Carbohydrates - administration & dosage; Dietary Fats - administration & dosage; Dietary Fiber - administration & dosage; Dietary Proteins - administration & dosage; Energy Intake; Female; Fibroblast Growth Factors - genetics; Fibroblast Growth Factors - metabolism; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Linear Models; Male; NF-kappa B - genetics; NF-kappa B - metabolism; Obesity - genetics; Polymorphism, Single Nucleotide
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddt032

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.