@article{b2fe0b5c3d2e4ad2b32b11f72c447de0,
title = "A missense variant in mitochondrial amidoxime reducing component 1 gene and protection against liver disease",
abstract = "Analyzing 12,361 all-cause cirrhosis cases and 790,095 controls from eight cohorts, we identify a common missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.91, p = 2.3∗10-11). This same variant also associates with lower levels of hepatic fat on computed tomographic imaging and lower odds of physician-diagnosed fatty liver as well as lower blood levels of alanine transaminase (-0.025 SD, 3.7∗10-43), alkaline phosphatase (-0.025 SD, 1.2∗10-37), total cholesterol (-0.030 SD, p = 1.9∗10-36) and LDL cholesterol (-0.027 SD, p = 5.1∗10-30) levels. We identified a series of additional MARC1 alleles (lowfrequency missense p.M187K and rare protein-truncating p.R200Ter) that also associated with lower cholesterol levels, liver enzyme levels and reduced risk of cirrhosis (0 cirrhosis cases for 238 R200Ter carriers versus 17,046 cases of cirrhosis among 759,027 non-carriers, p = 0.04) suggesting that deficiency of the MARC1 enzyme may lower blood cholesterol levels and protect against cirrhosis.",
author = "{Million Veteran Program} and Emdin, {Connor A.} and Haas, {Mary E.} and Khera, {Amit V.} and Krishna Aragam and Mark Chaffin and Derek Klarin and George Hindy and Lan Jiang and Wei, {Wei Qi} and Qiping Feng and Juha Karjalainen and Aki Havulinna and Tuomo Kiiskinen and Alexander Bick and Diego Ardissino and Wilson, {James G.} and Heribert Schunkert and Ruth McPherson and Hugh Watkins and Roberto Elosua and Bown, {Matthew J.} and Samani, {Nilesh J.} and Usman Baber and Jeanette Erdmann and Namrata Gupta and John Danesh and Danish Saleheen and Chang, {Kyong Mi} and Marijana Vujkovic and Ben Voight and Scott Damrauer and Julie Lynch and David Kaplan and Marina Serper and Philip Tsao and Josep Mercader and Craig Hanis and Mark Daly and Joshua Denny and Stacey Gabriel and Sekar Kathiresan",
note = "Publisher Copyright: {\textcopyright} 2020 Emdin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2020",
month = apr,
doi = "10.1371/journal.pgen.1008629",
language = "English",
volume = "16",
journal = "PLoS Genetics",
issn = "1553-7390",
publisher = "Public Library of Science",
number = "4",
}