Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 (low-frequency 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.

Original publication

DOI

10.1371/journal.pgen.1008629

Type

Journal article

Journal

PLoS genetics

Publication Date

13/04/2020

Volume

16

Pages

e1008629 - e1008629

Addresses

Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

Keywords

Million Veteran Program, Liver, Humans, Fatty Liver, Liver Cirrhosis, Liver Cirrhosis, Alcoholic, Genetic Predisposition to Disease, Oxidoreductases, Mitochondrial Proteins, Homozygote, Mutation, Missense, Alleles, Middle Aged, Female, Male, Cholesterol, LDL, Coronary Artery Disease, Datasets as Topic, Loss of Function Mutation