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

Jordi Merino; Hassan S. Dashti; Sherly X. Li; Chloé Sarnowski; Anne E. Justice; Misa Graff; Constantina Papoutsakis; Caren E. Smith; George V. Dedoussis; Rozenn N. Lemaitre; Mary K. Wojczynski; Satu Männistö; Julius S. Ngwa; Minjung Kho; Tarunveer S. Ahluwalia; Natalia Pervjakova; Denise K. Houston; Claude Bouchard; Tao Huang; Marju Orho-Melander; Alexis C. Frazier-Wood; Dennis O. Mook-Kanamori; Louis Pérusse; Craig E. Pennell; Paul S. de Vries; Trudy Voortman; Olivia Li; Stavroula Kanoni; Lynda M. Rose; Terho Lehtimäki; Jing Hua Zhao; Mary F. Feitosa; Jian’an Luan; Nicola M. McKeown; Jennifer A. Smith; Torben Hansen; Niina Eklund; Mike A. Nalls; Tuomo Rankinen; Jinyan Huang; Dena G. Hernandez; Christina Alexandra Schulz; Ani Manichaikul; Ruifang Li-Gao; Marie Claude Vohl; Carol A. Wang; Frank J.A. van Rooij; Jean Shin; Ioanna P. Kalafati; Felix Day; Paul M. Ridker; Mika Kähönen; David S. Siscovick; Claudia Langenberg; Wei Zhao; Arne Astrup; Paul Knekt; Melissa Garcia; D. C. Rao; Qibin Qi; Luigi Ferrucci; Ulrika Ericson; John Blangero; Albert Hofman; Zdenka Pausova; Vera Mikkilä; Nick J. Wareham; Sharon L.R. Kardia; Oluf Pedersen; Antti Jula; Joanne E. Curran; M. Carola Zillikens; Jorma S. Viikari; Nita G. Forouhi; José M. Ordovás; John C. Lieske; Harri Rissanen; André G. Uitterlinden; Olli T. Raitakari; Jessica C. Kiefte-de Jong; Josée Dupuis; Jerome I. Rotter; Kari E. North; Robert A. Scott; Michael A. Province; Markus Perola; L. Adrienne Cupples; Stephen T. Turner; Thorkild I.A. Sørensen; Veikko Salomaa; Yongmei Liu; Yun J. Sung; Lu Qi; Stefania Bandinelli; Stephen S. Rich; Renée de Mutsert; Angelo Tremblay; Wendy H. Oddy; Oscar H. Franco; Tomas Paus; Jose C. Florez; Panos Deloukas; Leo Pekka Lyytikäinen; Daniel I. Chasman; Audrey Y. Chu; Toshiko Tanaka

doi:10.1038/s41380-018-0079-4

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

Jordi Merino, Hassan S. Dashti, Sherly X. Li, Chloé Sarnowski, Anne E. Justice, Misa Graff, Constantina Papoutsakis, Caren E. Smith, George V. Dedoussis, Rozenn N. Lemaitre, Mary K. Wojczynski, Satu Männistö, Julius S. Ngwa, Minjung Kho, Tarunveer S. Ahluwalia, Natalia Pervjakova, Denise K. Houston, Claude Bouchard, Tao Huang, Marju Orho-MelanderAlexis C. Frazier-Wood, Dennis O. Mook-Kanamori, Louis Pérusse, Craig E. Pennell, Paul S. de Vries, Trudy Voortman, Olivia Li, Stavroula Kanoni, Lynda M. Rose, Terho Lehtimäki, Jing Hua Zhao, Mary F. Feitosa, Jian’an Luan, Nicola M. McKeown, Jennifer A. Smith, Torben Hansen, Niina Eklund, Mike A. Nalls, Tuomo Rankinen, Jinyan Huang, Dena G. Hernandez, Christina Alexandra Schulz, Ani Manichaikul, Ruifang Li-Gao, Marie Claude Vohl, Carol A. Wang, Frank J.A. van Rooij, Jean Shin, Ioanna P. Kalafati, Felix Day, Paul M. Ridker, Mika Kähönen, David S. Siscovick, Claudia Langenberg, Wei Zhao, Arne Astrup, Paul Knekt, Melissa Garcia, D. C. Rao, Qibin Qi, Luigi Ferrucci, Ulrika Ericson, John Blangero, Albert Hofman, Zdenka Pausova, Vera Mikkilä, Nick J. Wareham, Sharon L.R. Kardia, Oluf Pedersen, Antti Jula, Joanne E. Curran, M. Carola Zillikens, Jorma S. Viikari, Nita G. Forouhi, José M. Ordovás, John C. Lieske, Harri Rissanen, André G. Uitterlinden, Olli T. Raitakari, Jessica C. Kiefte-de Jong, Josée Dupuis, Jerome I. Rotter, Kari E. North, Robert A. Scott, Michael A. Province, Markus Perola, L. Adrienne Cupples, Stephen T. Turner, Thorkild I.A. Sørensen, Veikko Salomaa, Yongmei Liu, Yun J. Sung, Lu Qi, Stefania Bandinelli, Stephen S. Rich, Renée de Mutsert, Angelo Tremblay, Wendy H. Oddy, Oscar H. Franco, Tomas Paus, Jose C. Florez, Panos Deloukas, Leo Pekka Lyytikäinen, Daniel I. Chasman, Audrey Y. Chu, Toshiko Tanaka

Nephrology and Hypertension

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

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 × 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.

Original language	English (US)
Pages (from-to)	1920-1932
Number of pages	13
Journal	Molecular Psychiatry
Volume	24
Issue number	12
DOIs	https://doi.org/10.1038/s41380-018-0079-4
State	Published - Dec 1 2019

ASJC Scopus subject areas

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Molecular Biology

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10.1038/s41380-018-0079-4

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Merino, J., Dashti, H. S., Li, S. X., Sarnowski, C., Justice, A. E., Graff, M., Papoutsakis, C., Smith, C. E., Dedoussis, G. V., Lemaitre, R. N., Wojczynski, M. K., Männistö, S., Ngwa, J. S., Kho, M., Ahluwalia, T. S., Pervjakova, N., Houston, D. K., Bouchard, C., Huang, T., ... Tanaka, T. (2019). 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. Molecular Psychiatry, 24(12), 1920-1932. https://doi.org/10.1038/s41380-018-0079-4

Merino, J, Dashti, HS, Li, SX, Sarnowski, C, Justice, AE, Graff, M, Papoutsakis, C, Smith, CE, Dedoussis, GV, Lemaitre, RN, Wojczynski, MK, Männistö, S, Ngwa, JS, Kho, M, Ahluwalia, TS, Pervjakova, N, Houston, DK, Bouchard, C, Huang, T, Orho-Melander, M, Frazier-Wood, AC, Mook-Kanamori, DO, Pérusse, L, Pennell, CE, de Vries, PS, Voortman, T, Li, O, Kanoni, S, Rose, LM, Lehtimäki, T, Zhao, JH, Feitosa, MF, Luan, J, McKeown, NM, Smith, JA, Hansen, T, Eklund, N, Nalls, MA, Rankinen, T, Huang, J, Hernandez, DG, Schulz, CA, Manichaikul, A, Li-Gao, R, Vohl, MC, Wang, CA, van Rooij, FJA, Shin, J, Kalafati, IP, Day, F, Ridker, PM, Kähönen, M, Siscovick, DS, Langenberg, C, Zhao, W, Astrup, A, Knekt, P, Garcia, M, Rao, DC, Qi, Q, Ferrucci, L, Ericson, U, Blangero, J, Hofman, A, Pausova, Z, Mikkilä, V, Wareham, NJ, Kardia, SLR, Pedersen, O, Jula, A, Curran, JE, Zillikens, MC, Viikari, JS, Forouhi, NG, Ordovás, JM, Lieske, JC, Rissanen, H, Uitterlinden, AG, Raitakari, OT, Kiefte-de Jong, JC, Dupuis, J, Rotter, JI, North, KE, Scott, RA, Province, MA, Perola, M, Cupples, LA, Turner, ST, Sørensen, TIA, Salomaa, V, Liu, Y, Sung, YJ, Qi, L, Bandinelli, S, Rich, SS, de Mutsert, R, Tremblay, A, Oddy, WH, Franco, OH, Paus, T, Florez, JC, Deloukas, P, Lyytikäinen, LP, Chasman, DI, Chu, AY & Tanaka, T 2019, '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', Molecular Psychiatry, vol. 24, no. 12, pp. 1920-1932. https://doi.org/10.1038/s41380-018-0079-4

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title = "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",

abstract = "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 × 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.",

author = "Jordi Merino and Dashti, {Hassan S.} and Li, {Sherly X.} and Chlo{\'e} Sarnowski and Justice, {Anne E.} and Misa Graff and Constantina Papoutsakis and Smith, {Caren E.} and Dedoussis, {George V.} and Lemaitre, {Rozenn N.} and Wojczynski, {Mary K.} and Satu M{\"a}nnist{\"o} and Ngwa, {Julius S.} and Minjung Kho and Ahluwalia, {Tarunveer S.} and Natalia Pervjakova and Houston, {Denise K.} and Claude Bouchard and Tao Huang and Marju Orho-Melander and Frazier-Wood, {Alexis C.} and Mook-Kanamori, {Dennis O.} and Louis P{\'e}russe and Pennell, {Craig E.} and {de Vries}, {Paul S.} and Trudy Voortman and Olivia Li and Stavroula Kanoni and Rose, {Lynda M.} and Terho Lehtim{\"a}ki and Zhao, {Jing Hua} and Feitosa, {Mary F.} and Jian{\textquoteright}an Luan and McKeown, {Nicola M.} and Smith, {Jennifer A.} and Torben Hansen and Niina Eklund and Nalls, {Mike A.} and Tuomo Rankinen and Jinyan Huang and Hernandez, {Dena G.} and Schulz, {Christina Alexandra} and Ani Manichaikul and Ruifang Li-Gao and Vohl, {Marie Claude} and Wang, {Carol A.} and {van Rooij}, {Frank J.A.} and Jean Shin and Kalafati, {Ioanna P.} and Felix Day and Ridker, {Paul M.} and Mika K{\"a}h{\"o}nen and Siscovick, {David S.} and Claudia Langenberg and Wei Zhao and Arne Astrup and Paul Knekt and Melissa Garcia and Rao, {D. C.} and Qibin Qi and Luigi Ferrucci and Ulrika Ericson and John Blangero and Albert Hofman and Zdenka Pausova and Vera Mikkil{\"a} and Wareham, {Nick J.} and Kardia, {Sharon L.R.} and Oluf Pedersen and Antti Jula and Curran, {Joanne E.} and Zillikens, {M. Carola} and Viikari, {Jorma S.} and Forouhi, {Nita G.} and Ordov{\'a}s, {Jos{\'e} M.} and Lieske, {John C.} and Harri Rissanen and Uitterlinden, {Andr{\'e} G.} and Raitakari, {Olli T.} and {Kiefte-de Jong}, {Jessica C.} and Jos{\'e}e Dupuis and Rotter, {Jerome I.} and North, {Kari E.} and Scott, {Robert A.} and Province, {Michael A.} and Markus Perola and Cupples, {L. Adrienne} and Turner, {Stephen T.} and S{\o}rensen, {Thorkild I.A.} and Veikko Salomaa and Yongmei Liu and Sung, {Yun J.} and Lu Qi and Stefania Bandinelli and Rich, {Stephen S.} and {de Mutsert}, Ren{\'e}e and Angelo Tremblay and Oddy, {Wendy H.} and Franco, {Oscar H.} and Tomas Paus and Florez, {Jose C.} and Panos Deloukas and Lyytik{\"a}inen, {Leo Pekka} and Chasman, {Daniel I.} and Chu, {Audrey Y.} and Toshiko Tanaka",

note = "Publisher Copyright: {\textcopyright} 2018, Macmillan Publishers Limited, part of Springer Nature.",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41380-018-0079-4",

language = "English (US)",

volume = "24",

pages = "1920--1932",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "12",

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TY - JOUR

T1 - 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

AU - Merino, Jordi

AU - Dashti, Hassan S.

AU - Li, Sherly X.

AU - Sarnowski, Chloé

AU - Justice, Anne E.

AU - Graff, Misa

AU - Papoutsakis, Constantina

AU - Smith, Caren E.

AU - Dedoussis, George V.

AU - Lemaitre, Rozenn N.

AU - Wojczynski, Mary K.

AU - Männistö, Satu

AU - Ngwa, Julius S.

AU - Kho, Minjung

AU - Ahluwalia, Tarunveer S.

AU - Pervjakova, Natalia

AU - Houston, Denise K.

AU - Bouchard, Claude

AU - Huang, Tao

AU - Orho-Melander, Marju

AU - Frazier-Wood, Alexis C.

AU - Mook-Kanamori, Dennis O.

AU - Pérusse, Louis

AU - Pennell, Craig E.

AU - de Vries, Paul S.

AU - Voortman, Trudy

AU - Li, Olivia

AU - Kanoni, Stavroula

AU - Rose, Lynda M.

AU - Lehtimäki, Terho

AU - Zhao, Jing Hua

AU - Feitosa, Mary F.

AU - Luan, Jian’an

AU - McKeown, Nicola M.

AU - Smith, Jennifer A.

AU - Hansen, Torben

AU - Eklund, Niina

AU - Nalls, Mike A.

AU - Rankinen, Tuomo

AU - Huang, Jinyan

AU - Hernandez, Dena G.

AU - Schulz, Christina Alexandra

AU - Manichaikul, Ani

AU - Li-Gao, Ruifang

AU - Vohl, Marie Claude

AU - Wang, Carol A.

AU - van Rooij, Frank J.A.

AU - Shin, Jean

AU - Kalafati, Ioanna P.

AU - Day, Felix

AU - Ridker, Paul M.

AU - Kähönen, Mika

AU - Siscovick, David S.

AU - Langenberg, Claudia

AU - Zhao, Wei

AU - Astrup, Arne

AU - Knekt, Paul

AU - Garcia, Melissa

AU - Rao, D. C.

AU - Qi, Qibin

AU - Ferrucci, Luigi

AU - Ericson, Ulrika

AU - Blangero, John

AU - Hofman, Albert

AU - Pausova, Zdenka

AU - Mikkilä, Vera

AU - Wareham, Nick J.

AU - Kardia, Sharon L.R.

AU - Pedersen, Oluf

AU - Jula, Antti

AU - Curran, Joanne E.

AU - Zillikens, M. Carola

AU - Viikari, Jorma S.

AU - Forouhi, Nita G.

AU - Ordovás, José M.

AU - Lieske, John C.

AU - Rissanen, Harri

AU - Uitterlinden, André G.

AU - Raitakari, Olli T.

AU - Kiefte-de Jong, Jessica C.

AU - Dupuis, Josée

AU - Rotter, Jerome I.

AU - North, Kari E.

AU - Scott, Robert A.

AU - Province, Michael A.

AU - Perola, Markus

AU - Cupples, L. Adrienne

AU - Turner, Stephen T.

AU - Sørensen, Thorkild I.A.

AU - Salomaa, Veikko

AU - Liu, Yongmei

AU - Sung, Yun J.

AU - Qi, Lu

AU - Bandinelli, Stefania

AU - Rich, Stephen S.

AU - de Mutsert, Renée

AU - Tremblay, Angelo

AU - Oddy, Wendy H.

AU - Franco, Oscar H.

AU - Paus, Tomas

AU - Florez, Jose C.

AU - Deloukas, Panos

AU - Lyytikäinen, Leo Pekka

AU - Chasman, Daniel I.

AU - Chu, Audrey Y.

AU - Tanaka, Toshiko

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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 × 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.

AB - 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 × 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=85049629569&partnerID=8YFLogxK

U2 - 10.1038/s41380-018-0079-4

DO - 10.1038/s41380-018-0079-4

M3 - Article

C2 - 29988085

AN - SCOPUS:85049629569

SN - 1359-4184

VL - 24

SP - 1920

EP - 1932

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 12

ER -

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

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