Journal
HUMAN MOLECULAR GENETICS
Volume 23, Issue 25, Pages 6961-6972Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddu411
Keywords
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Funding
- Cancer Research UK [14136] Funding Source: Medline
- CIHR [GR-15187, MOP-77652] Funding Source: Medline
- FIC NIH HHS [TW05596, TW008288] Funding Source: Medline
- Medical Research Council [G0701863, MC_UU_12015/1, MC_UU_12015/5, MC_UP_A620_1014, MC_UP_A100_1003, MC_U106179471, MC_U147585824, G0401527, G1000143, MC_UU_12011/1] Funding Source: Medline
- NCATS NIH HHS [UL1 TR000124, UL1TR000124] Funding Source: Medline
- NCI NIH HHS [R01CA064277, R37CA070867, U54CA155626, R01CA122364, UM1 CA182910, CA047988, R01CA092585, R01 CA148667, R01CA124558, P30 CA016086, R01CA148667, CA055075, CA87969, R01CA82729, UM1 CA173640, CA49449, R01CA082729] Funding Source: Medline
- NCRR NIH HHS [RR20649, RR-024156, UL1RR025005] Funding Source: Medline
- NEI NIH HHS [R01 EY015473, EY015473] Funding Source: Medline
- NHGRI NIH HHS [U01 HG004728, HHSN268200782096C, U01HG004399, U01HG004402, U01HG004728-02] Funding Source: Medline
- NHLBI NIH HHS [N01HC85086, R01 HL034594, HHSN268201100012C, R01HL087641, HL085144, R21 HL126024, N01HC85079, N01HC85081, R01HL071205, R01 HL105756, R01HL071252, HL120393, HL087652, N01-HC-95159, HL088521, HHSN268201100011C, N01-HC-95169, HL073168, HL34594, N01HC55222, N02-HL-6-4278, N01-HC-25195, HHSN268201100008C, R01 HL103612, 5R01 HL08770003, HL043851, R01 HL120393, HL-45670, R01HL59367, N01HC85080, R01HL085710, HL105756, 5R01 HL08821502, HHSN268201100007C, HL085251, N02‐HL‐6‐4278, HHSN268201200036C, R01HL086694, K08 HL112845, HHSN268201100010C, R01HL071250, R01HL071051, R01HL071258, HL103612, R01 HL117078, R01HL071251, HL071981, R01HL071259, HHSN268200800007C, N01HC85083, HHSN268201100006C, HL080295, HHSN268201100009C, HL080467, N01HC85082, HHSN268201100005C] Funding Source: Medline
- NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, AG023629, N01-AG-6-2101, R01-AG032098] Funding Source: Medline
- NIDDK NIH HHS [R01 DK091718, DK080140, DK063491, 5P30DK46200, DK58845, DK70756, 5R01 DK06833603, R01 DK078150, DK091718, DK46200, 5R01 DK07568102, DK078150, DK56350, R01 DK089256, P30 DK046200] Funding Source: Medline
- NIEHS NIH HHS [ES10126, P30 ES010126] Funding Source: Medline
- NIMHD NIH HHS [263 MD 9164, 263 MD 821336] Funding Source: Medline
- PHS HHS [HHSN268200625226C] Funding Source: Medline
- MRC [MC_UU_12015/1, MC_UU_12015/5, MC_UP_A100_1003, G0701863] Funding Source: UKRI
- Cancer Research UK [14136] Funding Source: researchfish
- Medical Research Council [G0701863, MC_UP_A620_1014, MC_UU_12011/1, G0401527, G1000143, U1475000001, MC_UU_12015/1, MC_UP_A100_1003, MC_U147585824, MC_U106179471, MC_UU_12015/5] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0508-10082, NF-SI-0512-10135, NF-SI-0512-10114, NF-SI-0513-10085] Funding Source: researchfish
- Novo Nordisk Fonden [NNF14OC0011049] Funding Source: researchfish
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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 BM I. 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 x 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 x 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 x 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 x 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.
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