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

Qibin Qi; Tuomas O Kilpeläinen; Mary K Downer; Toshiko Tanaka; Caren E Smith; Ivonne Sluijs; Emily Sonestedt; Audrey Y Chu; Frida Renström; Xiaochen Lin; Lars H Ängquist; Jinyan Huang; Zhonghua Liu; Yanping Li; Muhammad Asif Ali; Min Xu; Tarunveer Singh Ahluwalia; Jolanda M A Boer; Peng Chen; Makoto Daimon; Johan Eriksson; Markus Perola; Yechiel Friedlander; Yu-Tang Gao; Denise H M Heppe; John W Holloway; Denise K Houston; Stavroula Kanoni; Yu-Mi Kim; Maarit A Laaksonen; Tiina Jääskeläinen; Nanette R Lee; Terho Lehtimäki; Rozenn N Lemaitre; Wei Lu; Robert N Luben; Ani Manichaikul; Satu Männistö; Pedro Marques-Vidal; Keri L Monda; Julius S Ngwa; Louis Perusse; Frank J A van Rooij; Yong-Bing Xiang; Wanqing Wen; Mary K Wojczynski; Jingwen Zhu; Ingrid B Borecki; Claude Bouchard; Qiuyin Cai; Cyrus Cooper; George V Dedoussis; Panos Deloukas; Luigi Ferrucci; Nita G Forouhi; Torben Hansen; Lene Christiansen; Albert Hofman; Ingegerd Johansson; Torben Jørgensen; Shigeru Karasawa; Kay-Tee Khaw; Mi-Kyung Kim; Kati Kristiansson; Huaixing Li; Xu Lin; Yongmei Liu; Kurt K Lohman; Jirong Long; Vera Mikkilä; Dariush Mozaffarian; Kari North; Oluf Pedersen; Olli Raitakari; Harri Rissanen; Jaakko Tuomilehto; Yvonne T van der Schouw; André G Uitterlinden; M Carola Zillikens; Oscar H Franco; E Shyong Tai; Xiao Ou Shu; David S Siscovick; Ulla Toft; W M Monique Verschuren; Peter Vollenweider; Nicholas J Wareham; Jacqueline C M Witteman; Wei Zheng; Paul M Ridker; Jae H Kang; Liming Liang; Majken K Jensen; Gary C Curhan; Louis R Pasquale; David J Hunter; Karen L Mohlke; Matti Uusitupa; L Adrienne Cupples; Tuomo Rankinen; Marju Orho-Melander; Tao Wang; Daniel I Chasman; Paul W Franks; Thorkild I A Sørensen; Frank B Hu; Ruth J F Loos; Jennifer A Nettleton; Lu Qi

doi:10.1093/hmg/ddu411

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

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

Qibin Qi, Tuomas O Kilpeläinen, Mary K Downer, Toshiko Tanaka, Caren E Smith, Ivonne Sluijs, Emily Sonestedt, Audrey Y Chu, Frida Renström, Xiaochen Lin, …

Human molecular genetics, Vol.23(25), pp.6961-6972

20/12/2014

DOI: https://doi.org/10.1093/hmg/ddu411

PMCID: PMC4271061

PMID: 25104851

Abstract

Adult

African Americans

Aged

Alleles

Alpha-Ketoglutarate-Dependent Dioxygenase FTO

Asians

Body Mass Index

Dietary Carbohydrates - administration & dosage

Dietary Fats - administration & dosage

Dietary Proteins - administration & dosage

Energy Intake - genetics

Female

Gene Frequency

Humans

Male

Middle Aged

Obesity - ethnology

Obesity - genetics

Obesity - metabolism

Obesity - pathology

Polymorphism, Single Nucleotide

Proteins - genetics

Whites

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.

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Title: FTO genetic variants, dietary intake and body mass index: insights from 177,330 individuals
Creators - without role: Qibin Qi - Albert Einstein College of Medicine
Tuomas O Kilpeläinen - Foundation Center
Mary K Downer - Nutrition 21
Toshiko Tanaka - National Institute on Aging
Caren E Smith - Tufts University
Ivonne Sluijs - University Medical Center Utrecht
Emily Sonestedt - Lund University
Audrey Y Chu - General Department of Preventive Medicine
Frida Renström - Lund University
Xiaochen Lin - Harvard University
Lars H Ängquist - Frederiksberg Hospital
Jinyan Huang - Shanghai Jiao Tong University
Zhonghua Liu - Harvard University
Yanping Li - Nutrition 21
Muhammad Asif Ali - Department of Nutrition and
Min Xu - Nutrition 21
Tarunveer Singh Ahluwalia - Copenhagen Prospective Studies on Asthma in Childhood
Jolanda M A Boer - National Institute for Public Health and the Environment
Peng Chen - Saw Swee Hock School of Public Health and
Makoto Daimon - Hirosaki University
Johan Eriksson - Finnish Institute for Health and Welfare
Markus Perola - Finnish Institute for Health and Welfare
Yechiel Friedlander - Hebrew University of Jerusalem
Yu-Tang Gao - Renji Hospital
Denise H M Heppe - Pediatrics and Genetics
John W Holloway - University of Southampton
Denise K Houston - Department of Internal Medicine, Section on Gerontology and Geriatric Medicine
Stavroula Kanoni - Queen Mary University of London
Yu-Mi Kim - Dong-A University
Maarit A Laaksonen - Finnish Institute for Health and Welfare
Tiina Jääskeläinen - University of Eastern Finland
Nanette R Lee - University of San Carlos
Terho Lehtimäki - Fimlab
Rozenn N Lemaitre - Cardiovascular Health Research Unit, Department of Medicine and
Wei Lu - Shanghai Institute of Disaster Prevention and Relief
Robert N Luben - University of Cambridge
Ani Manichaikul - University of Virginia
Satu Männistö - Finnish Institute for Health and Welfare
Pedro Marques-Vidal - Institute of Social and Preventive Medicine
Keri L Monda - Amgen
Julius S Ngwa - Boston University
Louis Perusse - Université Laval
Frank J A van Rooij - Netherlands Consortium for Healthy Ageing
Yong-Bing Xiang - Renji Hospital
Wanqing Wen - Vanderbilt University
Mary K Wojczynski - Washington University in St. Louis
Jingwen Zhu - Shanghai Institutes for Biological Sciences
Ingrid B Borecki - Washington University in St. Louis
Claude Bouchard - Pennington Biomedical Research Center
Qiuyin Cai - Vanderbilt University
Cyrus Cooper - University of Southampton
George V Dedoussis - Harokopio University of Athens
Panos Deloukas - Queen Mary University of London
Luigi Ferrucci - National Institute on Aging
Nita G Forouhi - University of Cambridge
Torben Hansen - Novo Nordisk Foundation
Lene Christiansen - University of Southern Denmark
Albert Hofman - Netherlands Consortium for Healthy Ageing
Ingegerd Johansson - Stomatology Hospital
Torben Jørgensen - Glostrup Hospital
Shigeru Karasawa - Yamagata University
Kay-Tee Khaw - University of Cambridge
Mi-Kyung Kim - Hanyang University
Kati Kristiansson - Finnish Institute for Health and Welfare
Huaixing Li - Shanghai Institutes for Biological Sciences
Xu Lin - Shanghai Institutes for Biological Sciences
Yongmei Liu - Faculty of Public Health
Kurt K Lohman - Wake Forest University
Jirong Long - Vanderbilt University
Vera Mikkilä - University of Helsinki
Dariush Mozaffarian - Tufts University
Kari North - Department of Epidemiology Carolina Center for Genome Sciences
Oluf Pedersen - Novo Nordisk Foundation
Olli Raitakari - Turku University Hospital
Harri Rissanen - Finnish Institute for Health and Welfare
Jaakko Tuomilehto - King Abdulaziz University
Yvonne T van der Schouw - University Medical Center Utrecht
André G Uitterlinden - Netherlands Consortium for Healthy Ageing
M Carola Zillikens - Erasmus MC
Oscar H Franco - Netherlands Consortium for Healthy Ageing
E Shyong Tai - Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore, Singapore
Xiao Ou Shu - Vanderbilt University School of Medicine
David S Siscovick - University of Washington
Ulla Toft - Glostrup Hospital
W M Monique Verschuren - National Institute for Public Health and the Environment
Peter Vollenweider - University Hospital of Lausanne
Nicholas J Wareham - University of Cambridge
Jacqueline C M Witteman - Netherlands Consortium for Healthy Ageing
Wei Zheng - Vanderbilt University
Paul M Ridker - General Department of Preventive Medicine
Jae H Kang - Channing Division of Network Medicine, Department of Medicine
Liming Liang - Harvard University
Majken K Jensen - Harvard University
Gary C Curhan - Harvard University
Louis R Pasquale - Massachusetts Eye and Ear Infirmary
David J Hunter - Harvard University
Karen L Mohlke - University of North Carolina at Chapel Hill
Matti Uusitupa - University of Eastern Finland
L Adrienne Cupples - Framingham Heart Study
Tuomo Rankinen - Pennington Biomedical Research Center
Marju Orho-Melander - Lund University
Tao Wang - Albert Einstein College of Medicine
Daniel I Chasman - Brigham and Women's Hospital
Paul W Franks - Umeå University
Thorkild I A Sørensen - Novo Nordisk Foundation
Frank B Hu - Department of Nutrition and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Channing Division of Network Medicine, Department of Medicine
Ruth J F Loos - University of Cambridge
Jennifer A Nettleton - Division of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas Health Science Center, Houston, TX, USA
Lu Qi - Department of Nutrition and Channing Division of Network Medicine, Department of Medicine nhlqi@channing.harvard.edu
Publication Details: Human molecular genetics, Vol.23(25), pp.6961-6972
Grant note: R01CA064277 / NCI NIH HHS DK70756 / NIDDK NIH HHS HL073168 / NHLBI NIH HHS HL085251 / NHLBI NIH HHS G0701863 / Medical Research Council R01 DK091718 / NIDDK NIH HHS R01HL085710 / NHLBI NIH HHS N02-HL-6-4278 / NHLBI NIH HHS HHSN268200782096C / NHGRI NIH HHS P30 ES010126 / NIEHS NIH HHS HL080467 / NHLBI NIH HHS R01 HL103612 / NHLBI NIH HHS R21 HL126024 / NHLBI NIH HHS HL087652 / NHLBI NIH HHS MC_UP_A620_1014 / Medical Research Council R01HL59367 / NHLBI NIH HHS HHSN268201100005C / NHLBI NIH HHS HHSN268201100010C / NHLBI NIH HHS R01CA148667 / NCI NIH HHS UM1 CA173640 / NCI NIH HHS R01HL071258 / NHLBI NIH HHS R01 DK078150 / NIDDK NIH HHS N01-HC-95159 / NHLBI NIH HHS R01-AG032098 / NIA NIH HHS EY015473 / NEI NIH HHS TW05596 / FIC NIH HHS R01CA122364 / NCI NIH HHS 263 MD 821336 / NIMHD NIH HHS N02‐HL‐6‐4278 / NHLBI NIH HHS R01 HL120393 / NHLBI NIH HHS MC_UU_12015/5 / Medical Research Council 5R01 HL08770003 / NHLBI NIH HHS U54CA155626 / NCI NIH HHS HL120393 / NHLBI NIH HHS RR20649 / NCRR NIH HHS R01 CA148667 / NCI NIH HHS N01HC85083 / NHLBI NIH HHS HHSN268201100012C / NHLBI NIH HHS RR-024156 / NCRR NIH HHS R01 HL117078 / NHLBI NIH HHS N01-HC-25195 / NHLBI NIH HHS 5R01 HL08821502 / NHLBI NIH HHS 14136 / Cancer Research UK R01HL086694 / NHLBI NIH HHS MC_U106179471 / Medical Research Council U01HG004402 / NHGRI NIH HHS U01HG004728-02 / NHGRI NIH HHS 5P30DK46200 / NIDDK NIH HHS HHSN268201200036C / NHLBI NIH HHS N01HC85082 / NHLBI NIH HHS UL1TR000124 / NCATS NIH HHS HL34594 / NHLBI NIH HHS HL088521 / NHLBI NIH HHS HL-45670 / NHLBI NIH HHS R01 DK089256 / NIDDK NIH HHS CA047988 / NCI NIH HHS U01HG004399 / NHGRI NIH HHS N01-AG-6-2103 / NIA NIH HHS HL043851 / NHLBI NIH HHS DK091718 / NIDDK NIH HHS DK080140 / NIDDK NIH HHS G1000143 / Medical Research Council TW008288 / FIC NIH HHS N01HC85079 / NHLBI NIH HHS R01HL071250 / NHLBI NIH HHS 5R01 DK07568102 / NIDDK NIH HHS HHSN268200625226C / PHS HHS CA87969 / NCI NIH HHS HHSN268201100007C / NHLBI NIH HHS ES10126 / NIEHS NIH HHS P30 CA016086 / NCI NIH HHS N01-HC-95169 / NHLBI NIH HHS MC_UU_12011/1 / Medical Research Council GR-15187 / CIHR 5R01 DK06833603 / NIDDK NIH HHS MOP-77652 / CIHR HHSN268201100011C / NHLBI NIH HHS R37CA070867 / NCI NIH HHS K08 HL112845 / NHLBI NIH HHS HL105756 / NHLBI NIH HHS MC_U147585824 / Medical Research Council MC_UU_12015/1 / Medical Research Council R01HL071251 / NHLBI NIH HHS R01 HL034594 / NHLBI NIH HHS R01CA82729 / NCI NIH HHS N01HC85081 / NHLBI NIH HHS CA49449 / NCI NIH HHS DK56350 / NIDDK NIH HHS DK58845 / NIDDK NIH HHS R01HL071252 / NHLBI NIH HHS G0401527 / Medical Research Council UM1 CA182910 / NCI NIH HHS N01HC85086 / NHLBI NIH HHS HL071981 / NHLBI NIH HHS R01HL087641 / NHLBI NIH HHS N01HC85080 / NHLBI NIH HHS N01-AG-6-2101 / NIA NIH HHS R01 EY015473 / NEI NIH HHS R01CA124558 / NCI NIH HHS R01CA082729 / NCI NIH HHS HL085144 / NHLBI NIH HHS HHSN268201100006C / NHLBI NIH HHS DK078150 / NIDDK NIH HHS P30 DK046200 / NIDDK NIH HHS R01CA092585 / NCI NIH HHS UL1 TR000124 / NCATS NIH HHS N01HC55222 / NHLBI NIH HHS HHSN268200800007C / NHLBI NIH HHS R01HL071205 / NHLBI NIH HHS N01-AG-6-2106 / NIA NIH HHS HL103612 / NHLBI NIH HHS UL1RR025005 / NCRR NIH HHS HHSN268201100008C / NHLBI NIH HHS CA055075 / NCI NIH HHS U01 HG004728 / NHGRI NIH HHS MC_UP_A100_1003 / Medical Research Council R01 HL105756 / NHLBI NIH HHS 263 MD 9164 / NIMHD NIH HHS R01HL071259 / NHLBI NIH HHS R01HL071051 / NHLBI NIH HHS HHSN268201100009C / NHLBI NIH HHS DK46200 / NIDDK NIH HHS HL080295 / NHLBI NIH HHS DK063491 / NIDDK NIH HHS AG023629 / NIA NIH HHS
Identifiers: 9937953708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article