@article{e3515fd709044ee5ac091652bafe4878,
title = "An exome array study of the plasma metabolome",
abstract = "The study of rare variants may enhance our understanding of the genetic determinants of the metabolome. Here, we analyze the association between 217 plasma metabolites and exome variants on the Illumina HumanExome Beadchip in 2,076 participants in the Framingham Heart Study, with replication in 1,528 participants of the Atherosclerosis Risk in Communities Study. We identify an association between GMPS and xanthosine using single variant analysis and associations between HAL and histidine, PAH and phenylalanine, and UPB1 and ureidopropionate using gene-based tests (P < 5 × 10-8 in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metabolism. Further, we show how an examination of variants across the spectrum of allele frequency highlights independent association signals at select loci and generates a more integrated view of metabolite heritability. These studies build on prior metabolomics genome wide association studies to provide a more complete picture of the genetic architecture of the plasma metabolome.",
author = "Rhee, {Eugene P.} and Qiong Yang and Bing Yu and Xuan Liu and Susan Cheng and Amy Deik and Pierce, {Kerry A.} and Kevin Bullock and Ho, {Jennifer E.} and Daniel Levy and Florez, {Jose C.} and Sek Kathiresan and Larson, {Martin G.} and Vasan, {Ramachandran S.} and Clish, {Clary B.} and Wang, {Thomas J.} and Eric Boerwinkle and O'Donnell, {Christopher J.} and Gerszten, {Robert E.}",
note = "Funding Information: This work was supported by NIH contracts N01-HC-25195, R01-DK-HL-081572, R01-DK-108159 (R.E.G. and T.J.W.), R01-HL-098280 (R.E.G.), R-01-HL-093328 (R.S.V.) and K08-DK-090142 (E.P.R.); funding for the exome array genotyping in the Framingham Heart Study was provided by the Division of Intramural Research of the National Heart, Lung and Blood Institute (D.L., C.J.O.). The Atherosclerosis Risk in Communities (ARIC) study is carried out as a collaborative study supported by the National Heart, Lung and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and HHSN268201100012C). Funding support for 'Building on GWAS for NHLBI-diseases: the US CHARGE consortium' was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). Metabolomic profiling in ARIC was supported by the National Genome Research Institute (HG004402). We thank the staff and participants of the FHS and ARIC study for their important contributions.",
year = "2016",
month = jul,
day = "25",
doi = "10.1038/ncomms12360",
language = "English (US)",
volume = "7",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}