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FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.

TitleFTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals.
Publication TypeJournal Article
Year of Publication2014
AuthorsQi Q, Kilpeläinen TO, Downer MK, et al.
Secondary AuthorsQi L
JournalHum Mol Genet
Volume23
Issue25
Pagination6961-72
Date Published2014 Dec 20
ISSN1460-2083
KeywordsAdult, African Americans, Aged, Alleles, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Asian Continental Ancestry Group, Body Mass Index, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Female, Gene Frequency, Humans, Male, Middle Aged, Obesity, Polymorphism, Single Nucleotide, Proteins
Abstract

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

DOI10.1093/hmg/ddu411
Alternate JournalHum Mol Genet
PubMed ID25104851
PubMed Central IDPMC4271061
Grant ListHL073168 / HL / NHLBI NIH HHS / United States
HL34594 / HL / NHLBI NIH HHS / United States
N01HC55222 / HC / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
DK078150 / DK / NIDDK NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
5P30DK46200 / DK / NIDDK NIH HHS / United States
5R01 HL08770003 / HL / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
U01 HG004728 / HG / NHGRI NIH HHS / United States
N01-AG-6-2101 / AG / NIA NIH HHS / United States
HL043851 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
TW008288 / TW / FIC NIH HHS / United States
MC_UP_A100_1003 / / Medical Research Council / United Kingdom
HL-45670 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
N01HC85080 / HC / NHLBI NIH HHS / United States
R01HL085710 / HL / NHLBI NIH HHS / United States
R01CA092585 / CA / NCI NIH HHS / United States
R01-AG032098 / AG / NIA NIH HHS / United States
5R01 HL08821502 / HL / NHLBI NIH HHS / United States
N02‐HL‐6‐4278 / HL / NHLBI NIH HHS / United States
EY015473 / EY / NEI NIH HHS / United States
HL085251 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
RR-024156 / RR / NCRR NIH HHS / United States
N01-AG-6-2103 / AG / NIA NIH HHS / United States
5R01 DK06833603 / DK / NIDDK NIH HHS / United States
263 MD 821336 / MD / NIMHD NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
CA87969 / CA / NCI NIH HHS / United States
DK58845 / DK / NIDDK NIH HHS / United States
R01CA148667 / CA / NCI NIH HHS / United States
HL088521 / HL / NHLBI NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
R01 DK091718 / DK / NIDDK NIH HHS / United States
N01-HC-95159 / HC / NHLBI NIH HHS / United States
G1000143 / / Medical Research Council / United Kingdom
R01CA82729 / CA / NCI NIH HHS / United States
UM1 CA173640 / CA / NCI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
CA49449 / CA / NCI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
U01HG004399 / HG / NHGRI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MOP-77652 / / Canadian Institutes of Health Research / Canada
ES10126 / ES / NIEHS NIH HHS / United States
R01HL071252 / HL / NHLBI NIH HHS / United States
R01CA122364 / CA / NCI NIH HHS / United States
HL120393 / HL / NHLBI NIH HHS / United States
R01CA064277 / CA / NCI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
MC_UU_12015/1 / / Medical Research Council / United Kingdom
TW05596 / TW / FIC NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
R01HL071205 / HL / NHLBI NIH HHS / United States
MC_UP_A620_1014 / / Medical Research Council / United Kingdom
MC_U106179471 / / Medical Research Council / United Kingdom
CA047988 / CA / NCI NIH HHS / United States
N01HC85081 / HC / NHLBI NIH HHS / United States
P30 DK046200 / DK / NIDDK NIH HHS / United States
DK56350 / DK / NIDDK NIH HHS / United States
GR-15187 / / Canadian Institutes of Health Research / Canada
RR20649 / RR / NCRR NIH HHS / United States
N01HC85079 / HC / NHLBI NIH HHS / United States
R21 HL126024 / HL / NHLBI NIH HHS / United States
5R01 DK07568102 / DK / NIDDK NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HL085144 / HL / NHLBI NIH HHS / United States
14136 / / Cancer Research UK / United Kingdom
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01 CA148667 / CA / NCI NIH HHS / United States
N01-HC-95169 / HC / NHLBI NIH HHS / United States
G0401527 / / Medical Research Council / United Kingdom
G0701863 / / Medical Research Council / United Kingdom
DK091718 / DK / NIDDK NIH HHS / United States
R01 HL034594 / HL / NHLBI NIH HHS / United States
N01HC85086 / HC / NHLBI NIH HHS / United States
R01 EY015473 / EY / NEI NIH HHS / United States
N01HC85082 / HC / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
U01HG004728-02 / HG / NHGRI NIH HHS / United States
N01-AG-6-2106 / AG / NIA NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
R37CA070867 / CA / NCI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
MC_UU_12011/1 / / Medical Research Council / United Kingdom
HL080467 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
MC_UU_12015/5 / / Medical Research Council / United Kingdom
HHSN268201200036C / / PHS HHS / United States
HHSN268200782096C / / PHS HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01HC85083 / HC / NHLBI NIH HHS / United States
CA055075 / CA / NCI NIH HHS / United States
R01HL071259 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01HL071251 / HL / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
HL071981 / HL / NHLBI NIH HHS / United States
R01CA124558 / CA / NCI NIH HHS / United States
HL103612 / HL / NHLBI NIH HHS / United States
UM1 CA182910 / CA / NCI NIH HHS / United States
R01HL071258 / HL / NHLBI NIH HHS / United States
263 MD 9164 / MD / NIMHD NIH HHS / United States
DK080140 / DK / NIDDK NIH HHS / United States
AG023629 / AG / NIA NIH HHS / United States
R01HL071051 / HL / NHLBI NIH HHS / United States
MC_U147585824 / / Medical Research Council / United Kingdom
DK70756 / DK / NIDDK NIH HHS / United States
R01HL071250 / HL / NHLBI NIH HHS / United States
R01 DK078150 / DK / NIDDK NIH HHS / United States
K08 HL112845 / HL / NHLBI NIH HHS / United States
DK46200 / DK / NIDDK NIH HHS / United States
R01CA082729 / CA / NCI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
U54CA155626 / CA / NCI NIH HHS / United States