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.

Mol Psychiatry
Authors
Keywords
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) 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.

Year of Publication
2019
Journal
Mol Psychiatry
Volume
24
Issue
12
Pages
1920-1932
Date Published
2019 12
ISSN
1476-5578
DOI
10.1038/s41380-018-0079-4
PubMed ID
29988085
PubMed Central ID
PMC6326896
Links
Grant list
K24 DK110550 / DK / NIDDK NIH HHS / United States
T32 EY022303 / EY / NEI NIH HHS / United States
MC_QA137853 / MRC_ / Medical Research Council / United Kingdom
N01 HC025195 / HC / NHLBI NIH HHS / United States
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
U01 AG023746 / AG / NIA NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
K08 HL112845 / HL / NHLBI NIH HHS / United States
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
R01 HL119443 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
MC_UU_12015/5 / MRC_ / Medical Research Council / United Kingdom
RG/14/5/30893 / BHF_ / British Heart Foundation / United Kingdom
MC_PC_17228 / MRC_ / Medical Research Council / United Kingdom
U01 CA182913 / CA / NCI NIH HHS / United States