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, Y. 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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Jul 9 2018
Externally publishedYes

Fingerprint

Meta-Analysis
Epidemiology
Carbohydrates
Genome
Genetic Loci
Metabolic Diseases
Research
Sample Size
Adipose Tissue
Proteins
Obesity
Fats
Phenotype
Brain
fibroblast growth factor 21

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

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

In: Molecular Psychiatry, 09.07.2018, p. 1-13.

Research output: Contribution to journalArticle

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 2018, '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, pp. 1-13. https://doi.org/10.1038/s41380-018-0079-4
Merino, Jordi ; Dashti, Hassan S. ; Li, Sherly X. ; Sarnowski, Chloé ; Justice, Anne E. ; Graff, Misa ; Papoutsakis, Constantina ; Smith, Caren E. ; Dedoussis, George V. ; Lemaitre, Rozenn N. ; Wojczynski, Mary K. ; Männistö, Satu ; Ngwa, Julius S. ; Kho, Minjung ; Ahluwalia, Tarunveer S. ; Pervjakova, Natalia ; Houston, Denise K. ; Bouchard, Claude ; Huang, Tao ; Orho-Melander, Marju ; Frazier-Wood, Alexis C. ; Mook-Kanamori, Dennis O. ; Pérusse, Louis ; Pennell, Craig E. ; de Vries, Paul S. ; Voortman, Trudy ; Li, Olivia ; Kanoni, Stavroula ; Rose, Lynda M. ; Lehtimäki, Terho ; Zhao, Jing Hua ; Feitosa, Mary F. ; Luan, Jian’an ; McKeown, Nicola M. ; Smith, Jennifer A. ; Hansen, Torben ; Eklund, Niina ; Nalls, Mike A. ; Rankinen, Tuomo ; Huang, Jinyan ; Hernandez, Dena G. ; Schulz, Christina Alexandra ; Manichaikul, Ani ; Li-Gao, Ruifang ; Vohl, Marie Claude ; Wang, Carol A. ; van Rooij, Frank J.A. ; Shin, Jean ; Kalafati, Ioanna P. ; Day, Felix ; Ridker, Paul M. ; Kähönen, Mika ; Siscovick, David S. ; Langenberg, Claudia ; Zhao, Wei ; Astrup, Arne ; Knekt, Paul ; Garcia, Melissa ; Rao, D. C. ; Qi, Qibin ; Ferrucci, Luigi ; Ericson, Ulrika ; Blangero, John ; Hofman, Albert ; Pausova, Zdenka ; Mikkilä, Vera ; Wareham, Nick J. ; Kardia, Sharon L.R. ; Pedersen, Oluf ; Jula, Antti ; Curran, Joanne E. ; Zillikens, M. Carola ; Viikari, Jorma S. ; Forouhi, Nita G. ; Ordovás, José M. ; Lieske, John C. ; Rissanen, Harri ; Uitterlinden, André G. ; Raitakari, Olli T. ; Kiefte-de Jong, Jessica C. ; Dupuis, Josée ; Rotter, Jerome I. ; North, Kari E. ; Scott, Robert A. ; Province, Michael A. ; Perola, Markus ; Cupples, L. Adrienne ; Turner, Stephen T. ; Sørensen, Thorkild I.A. ; Salomaa, Veikko ; Liu, Yongmei ; Sung, Y. J. ; Qi, Lu ; Bandinelli, Stefania ; Rich, Stephen S. ; de Mutsert, Renée ; Tremblay, Angelo ; Oddy, Wendy H. ; Franco, Oscar H. ; Paus, Tomas ; Florez, Jose C. ; Deloukas, Panos ; Lyytikäinen, Leo Pekka ; Chasman, Daniel I. ; Chu, Audrey Y. ; Tanaka, Toshiko. / 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. In: Molecular Psychiatry. 2018 ; pp. 1-13.
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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.",
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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, Y. 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 - 2018/7/9

Y1 - 2018/7/9

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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U2 - 10.1038/s41380-018-0079-4

DO - 10.1038/s41380-018-0079-4

M3 - Article

AN - SCOPUS:85049629569

SP - 1

EP - 13

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

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