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

被引：122

作者：

Qi, Qibin ^{[1
,2
]}

Kilpelainen, Tuomas O. ^{[4
,5
]}

Downer, Mary K. ^{[2
]}

Tanaka, Toshiko ^{[7
]}

Smith, Caren E. ^{[8
]}

Sluijs, Ivonne ^{[9
]}

Sonestedtl, Emily ^{[10
]}

Chull, Audrey Y. ^{[11
]}

Renstrom, Frida ^{[10
]}

Lin, Xiaochen ^{[3
]}

Angquist, Lars H. ^{[15
]}

Huang, Jinyan ^{[16
]}

Liu, Zhonghua ^{[3
]}

Li, Yanping ^{[2
]}

Ali, Muhammad Asif ^{[2
]}

Xu, Min ^{[2
]}

Ahluwalia, Tarunveer Singh ^{[5
,6
,17
]}

Boer, Jolanda M. A. ^{[18
]}

Chen, Peng ^{[19
]}

Daimon, Makoto ^{[21
,22
]}

Eriksson, Johan ^{[23
]}

Perola, Markus ^{[24
,26
,27
]}

Friedlander, Yechiel ^{[28
]}

Gao, Yu-Tang ^{[29
]}

Heppe, Denise H. M. ^{[30
,31
,32
]}

Holloway, John W. ^{[34
]}

Houston, Denise K. ^{[35
]}

Kanoni, Stavroula ^{[38
]}

Kim, Yu-Mi ^{[39
]}

Laaksonen, Maarit A. ^{[26
]}

Jaaskelainen, Tiina ^{[40
]}

Lee, Nanette R. ^{[41
]}

Lehtimaki, Terho ^{[42
,43
]}

Lemaitre, Rozenn N. ^{[44
]}

Lu, Wei ^{[46
]}

Luben, Robert N. ^{[47
]}

Manichaiku, Ani ^{[48
,49
]}

Mannisto, Satu ^{[26
]}

Marques-Vidal, Pedro ^{[50
,51
]}

Monda, Keri L. ^{[52
,55
]}

Ngwa, Julius S. ^{[56
]}

Perusse, Louis ^{[57
]}

van Rooij, Frank J. A. ^{[31
,58
]}

Xiang, Yong-Bing ^{[29
]}

Wen, Wanqing ^{[59
]}

Wojczynski, Mary K. ^{[60
]}

Zhu, Jingwen ^{[61
,62
]}

Borecki, Ingrid B. ^{[60
]}

Bouchard, Claude ^{[63
]}

Cai, Qiuyin ^{[59
]}

机构：

[1] Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10467 USA

[2] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[4] Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[5] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[6] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark

[7] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA

[8] Tufts Univ, Jean Mayer USDA HNRCA, Nutr & Genom Lab, Boston, MA 02111 USA

[9] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[10] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden

[11] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[12] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA

[13] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[14] Harvard Univ, Sch Med, Boston, MA USA

[15] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark

[16] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200030, Peoples R China

[17] Gentofte Univ Hosp, Danish Pediat Asthma Ctr, Copenhagen, Denmark

[18] Natl Inst Publ Hlth & Environm, Ctr Nutr Prevent & Hlth Serv, NL-3720 BA Bilthoven, Netherlands

[19] Natl Univ Hlth Syst, Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore

[20] Natl Univ Hlth Syst, Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore

[21] Hirosaki Univ, Grad Sch Med, Dept Endocrinol & Metab, Hirosaki, Aomori, Japan

[22] Yamagata Univ, Fac Med, Dept Neurol Hematol Metab Endocrinol & Diabetol, Yamagata 990, Japan

[23] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland

[24] Univ Helsinki, Inst Mol Med, Helsinki, Finland

[25] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland

[26] Natl Inst Hlth & Welf, Helsinki, Finland

[27] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[28] Hebrew Univ Jerusalem, Sch Publ Hlth, Jerusalem, Israel

[29] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China

[30] Erasmus MC, Generat Study Grp R, Rotterdam, Netherlands

[31] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[32] Erasmus MC, Dept Pediat, Rotterdam, Netherlands

[33] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[34] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England

[35] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA

[36] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol, Winston Salem, NC USA

[37] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA

[38] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England

[39] Dong A Univ, Coll Med, Dept Prevent Med, Pusan, South Korea

[40] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland

[41] Univ San Carlos, U5C Off Populat Studies Fdn Inc, Cebu, Philippines

[42] Univ Tampere, Dept Clin Chem, Fimlab Labs, FIN-33101 Tampere, Finland

[43] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland

[44] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA

[45] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[46] Shanghai Inst Prevent Med, Shanghai, Peoples R China

[47] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England

[48] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA

[49] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA

[50] Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland

来源：

HUMAN MOLECULAR GENETICS | 2014年 / 23卷 / 25期

基金：

英国医学研究理事会;

关键词：

OBESITY-ASSOCIATED GENE; FAT MASS; PHYSICAL-ACTIVITY; ENERGY-INTAKE; FOOD-INTAKE; METABOLIC-RATE; ASSOCIATION; RS9939609; GENOTYPE; RISK;

D O I：

10.1093/hmg/ddu411

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：6961 / 6972

页数：12

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