Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium

被引：51

作者：

Merino, Jordi ^{[1
,2
,3
,4
]}

Dashti, Hassan S. ^{[1
,2
,3
]}

Li, Sherly X. ^{[5
]}

Sarnowski, Chloe ^{[6
]}

Justice, Anne E. ^{[7
,8
]}

Graff, Misa ^{[8
]}

Papoutsakis, Constantina ^{[9
]}

Smith, Caren E. ^{[10
]}

Dedoussis, George V. ^{[11
]}

Lemaitre, Rozenn N. ^{[12
]}

Wojczynski, Mary K. ^{[13
]}

Mannisto, Satu ^{[14
]}

Ngwa, Julius S. ^{[6
,15
]}

Kho, Minjung ^{[16
]}

Ahluwalia, Tarunveer S. ^{[17
]}

Pervjakova, Natalia ^{[14
,18
,19
,20
]}

Houston, Denise K. ^{[21
]}

Bouchard, Claude ^{[22
]}

Huang, Tao ^{[23
]}

Orho-Melander, Marju ^{[24
]}

Frazier-Wood, Alexis C. ^{[25
]}

Mook-Kanamori, Dennis O. ^{[26
,27
]}

Perusse, Louis ^{[28
,29
]}

Pennell, Craig E. ^{[30
]}

de Vries, Paul S. ^{[31
]}

Voortman, Trudy ^{[32
]}

Li, Olivia ^{[33
]}

Kanoni, Stavroula ^{[34
]}

Rose, Lynda M. ^{[35
,36
]}

Lehtimaki, Terho ^{[37
]}

Zhao, Jing Hua ^{[5
]}

Feitosa, Mary F. ^{[13
]}

Luan, Jian'an ^{[5
]}

McKeown, Nicola M. ^{[38
]}

Smith, Jennifer A. ^{[16
]}

Hansen, Torben ^{[17
]}

Eklund, Niina ^{[14
]}

Nalls, Mike A. ^{[39
,40
]}

Rankinen, Tuomo ^{[22
]}

Huang, Jinyan ^{[41
]}

Hernandez, Dena G. ^{[40
]}

Schulz, Christina-Alexandra ^{[24
]}

Manichaikul, Ani ^{[42
]}

Li-Gao, Ruifang ^{[26
]}

Vohl, Marie-Claude ^{[29
,43
]}

Wang, Carol A. ^{[30
]}

van Rooij, Frank J. A. ^{[32
]}

Shin, Jean ^{[33
]}

Kalafati, Ioanna P. ^{[11
]}

Day, Felix ^{[5
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA

[2] Broad Inst MIT & Harvard, Program Metab, Cambridge, MA 02142 USA

[3] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[4] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA

[5] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England

[6] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA

[7] Geisinger Hlth Weis Ctr Res, Biomed & Translat Informat Inst, Danvilla, PA USA

[8] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[9] Acad Nutr & Dietet, Res Int & Sci Affairs, Chicago, IL USA

[10] Tufts Univ, USDA, Nutr & Genom, JM,HNRCA, Boston, MA 02111 USA

[11] Harokopio Univ, Sch Hlth Sci & Educ, Dept Dietet & Nutrit Sci, Athens, Greece

[12] Univ Washington, Dept Med, Seattle, WA USA

[13] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

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

[15] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[16] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA

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

[18] Univ Tartu, Inst Genom, Estonian Genome Ctr, Tartu, Estonia

[19] Univ Tartu, Inst Mol & Cell Biol, Dept Biotechnol, Tartu, Estonia

[20] Imperial Coll London, Dept Med, Div Diabet Endocrinol & Metab, Genom Common Dis, London, England

[21] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27101 USA

[22] Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA

[23] Peking Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Beijing, Peoples R China

[24] Lund Univ, Diabet Ctr, Dept Clin Sci, Malmo, Sweden

[25] USDA ARS, Childrens Nutr Res Ctr, Houston, TX USA

[26] Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands

[27] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands

[28] Laval Univ, Fac Med, Dept Kinesiol, Quebec City, PQ, Canada

[29] Inst Nutr & Funct Foods, Quebec City, PQ, Canada

[30] Univ Newcastle, Fac Med & Hlth, Sch Med & Publ Hlth, Callaghan, NSW, Australia

[31] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA

[32] Erasmus MC Univ Hosp, Dept Epidemiol, Rotterdam, Netherlands

[33] Univ Toronto, Translat Med, Hosp Sick Children, Toronto, ON, Canada

[34] Queen Mary Univ London, William Harvey Res Inst, London, England

[35] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA

[36] Harvard Med Sch, Boston, MA 02115 USA

[37] Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem,Fimlab Labs, Tampere, Finland

[38] Tufts Univ, USDA, Nutrit Epidemiol, JM,HNRCA, Boston, MA 02111 USA

[39] Data Tecn Int, Glen Echo, MD USA

[40] NIA, Lab Neurogenet, Bethesda, MD 20892 USA

[41] Shanghai Inst Hematol, Dept Bioinformat, Shanghai, Peoples R China

[42] Univ Virginia, Div Biostat & Epidemiol, Ctr Publ Hlth Genom, Charlottesville, VA USA

[43] Laval Univ, Sch Nutr, Montreal, PQ, Canada

[44] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA

[45] Harvard Med Sch, Boston, MA 02115 USA

[46] New York Acad Med, New York, NY USA

[47] Univ Copenhagen, Fac Sci, Dept Nutr Exercise & Sports, Copenhagen, Denmark

[48] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA

[49] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

[50] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA

来源：

MOLECULAR PSYCHIATRY | 2019年 / 24卷 / 12期

关键词：

GENETIC-VARIANTS; MENDELIAN RANDOMIZATION; FOOD-INTAKE; ASSOCIATION; INSIGHTS; OBESITY; ADULTS; ATLAS; FGF21;

D O I：

10.1038/s41380-018-0079-4

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：

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 x 10(-6)) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

引用

页码：1920 / 1932

页数：13

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