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 - Astrup, Arne

AU - Pedersen, Oluf Borbye

AU - Sørensen, Thorkild I.A.

AU - Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium

N1 - CURIS 2018 NEXS 236

PY - 2019

Y1 - 2019

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.

U2 - 10.1038/s41380-018-0079-4

DO - 10.1038/s41380-018-0079-4

M3 - Journal article

C2 - 29988085

AN - SCOPUS:85049629569

VL - 24

SP - 1920

EP - 1932

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

ER -