Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Mol Psychiatry
Authors
Keywords
Abstract

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P

Year of Publication
2015
Journal
Mol Psychiatry
Volume
20
Issue
5
Pages
647-56
Date Published
2015 May
ISSN
1476-5578
URL
DOI
10.1038/mp.2014.107
PubMed ID
25288136
PubMed Central ID
PMC4388784
Links
Grant list
U01 HG004728 / HG / NHGRI NIH HHS / United States
MC_UP_A100_1003 / Medical Research Council / United Kingdom
P60 AA011998 / AA / NIAAA NIH HHS / United States
RG/08/014/24067 / British Heart Foundation / United Kingdom
G1000143 / Medical Research Council / United Kingdom
MR/L003120/1 / Medical Research Council / United Kingdom
R01 NS075321 / NS / NINDS NIH HHS / United States
MC_UU_12015/1 / Medical Research Council / United Kingdom
MC_U106179471 / Medical Research Council / United Kingdom
R01 NS041509 / NS / NINDS NIH HHS / United States
14136 / Cancer Research UK / United Kingdom
G0401527 / Medical Research Council / United Kingdom
090532 / Wellcome Trust / United Kingdom
R01 EY015473 / EY / NEI NIH HHS / United States
UM1 CA182913 / CA / NCI NIH HHS / United States
MC_UU_12015/5 / Medical Research Council / United Kingdom
R01 HL117078 / HL / NHLBI NIH HHS / United States