Novel locus including FGF21 is associated with dietary macronutrient intake.
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.
Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA, USA.
Audrey Y
AY
Chu
Tsegaselassie
T
Workalemahu
Nina P
NP
Paynter
Lynda M
LM
Rose
Franco
F
Giulianini
Toshiko
T
Tanaka
Julius S
JS
Ngwa
Qibin
Q
Qi
Gary C
GC
Curhan
Eric B
EB
Rimm
David J
DJ
Hunter
Louis R
LR
Pasquale
Paul M
PM
Ridker
Frank B
FB
Hu
Daniel I
DI
Chasman
Lu
L
Qi
D015992:Body Mass Index; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004041:Dietary Fats / Q000008:administration & dosage*; D004043:Dietary Fiber / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D002149:Energy Intake; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004043:Dietary Fiber; D004044:Dietary Proteins; D016328:NF-kappa B; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors