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, Ulrika Ericson, Markus Perola

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

31 Citeringar (SciVal)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)1920-1932
Antal sidor13
TidskriftMolecular Psychiatry
Volym24
Utgåva12
Tidigt onlinedatum2018 juli 9
DOI
StatusPublished - 2019 dec.

Ämnesklassifikation (UKÄ)

  • Medicinsk genetik

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