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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 LU ; Dashti, Hassan S.; Li, Sherly X.; Sarnowski, Chloé; Justice, Anne E.; Graff, Misa; Papoutsakis, Constantina; Smith, Caren E.; Dedoussis, George V. and Lemaitre, Rozenn N., et al. (2018) In Molecular Psychiatry p.1-13
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,... (More)

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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Molecular Psychiatry
pages
13 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85049629569
ISSN
1359-4184
DOI
10.1038/s41380-018-0079-4
language
English
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yes
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e77b8bcf-81b5-4ac1-844e-322b30da0b5e
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2018-07-20 11:23:54
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2019-01-20 05:57:16
@article{e77b8bcf-81b5-4ac1-844e-322b30da0b5e,
  abstract     = {<p>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 &lt; 1 × 10<sup>−6</sup>) 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.</p>},
  author       = {Merino, Jordi and Dashti, Hassan S. and Li, Sherly X. and Sarnowski, Chloé and Justice, Anne E. and Graff, Misa and Papoutsakis, Constantina and Smith, Caren E. and Dedoussis, George V. and Lemaitre, Rozenn N. and Wojczynski, Mary K. and Männistö, Satu and Ngwa, Julius S. and Kho, Minjung and Ahluwalia, Tarunveer S. and Pervjakova, Natalia and Houston, Denise K. and Bouchard, Claude and Huang, Tao and Orho-Melander, Marju and Frazier-Wood, Alexis C. and Mook-Kanamori, Dennis O. and Pérusse, Louis and Pennell, Craig E. and de Vries, Paul S. and Voortman, Trudy and Li, Olivia and Kanoni, Stavroula and Rose, Lynda M. and Lehtimäki, Terho and Zhao, Jing Hua and Feitosa, Mary F. and Luan, Jian’an and McKeown, Nicola M. and Smith, Jennifer A. and Hansen, Torben and Eklund, Niina and Nalls, Mike A. and Rankinen, Tuomo and Huang, Jinyan and Hernandez, Dena G. and Schulz, Christina Alexandra and Manichaikul, Ani and Li-Gao, Ruifang and Vohl, Marie Claude and Wang, Carol A. and van Rooij, Frank J.A. and Shin, Jean and Ericson, Ulrika and Perola, Markus},
  issn         = {1359-4184},
  language     = {eng},
  month        = {07},
  pages        = {1--13},
  publisher    = {Nature Publishing Group},
  series       = {Molecular Psychiatry},
  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},
  url          = {http://dx.doi.org/10.1038/s41380-018-0079-4},
  year         = {2018},
}