PLoS GeneticsGenomicsPeer-reviewed journal article
A missense variant in Mitochondrial Amidoxime Reducing Component 1 gene and protection against liver disease
Connor A. EmdiniD, Mary E. HaasiD, Amit V. KheraiD, Krishna G. AragamiD, Mark D. ChaffiniD, Derek M. KlariniD, George HindyiD, Lan JiangiD, Wei‐Qi WeiiD, QiPing FengiD, Juha M KarjalaineniD, Aki Samuli HavulinnaiD, Tuomo KiiskineniD, Alexander G. BickiD, Diego ArdissinoiD, James G. WilsoniD, Heribert SchunkertiD, Ruth McPhersoniD, Hugh C WatkinsiD, Roberto ElosúaiD, Matthew J. BowniD, Nilesh J. SamaniiD, Usman BaberiD, Jeanette ErdmanniD, Namrata GuptaiD, , Sekar KathiresaniD
Abstract
Analyzing 5770 all-cause cirrhosis cases and 572,850 controls from seven cohorts, we identify a missense variant in the Mitochondrial Amidoxime Reducing Component 1 gene (MARC1 p.A165T) that associates with protection from all-cause cirrhosis (OR 0.88, p=2.1*10-8). 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 (-0.012 SD, 1.4*10-8), alkaline phosphatase (-0.019 SD, 6.6*10-9), total cholesterol (-0.037 SD, p=1*10-18) and LDL cholesterol (-0.035 SD, p=7.3*10-16). Carriers of rare protein-truncating variants in MARC1 had lower liver enzyme levels, cholesterol levels, and reduced odds of liver disease (OR 0.19, p= 0.04) suggesting that deficiency of the MARC1 enzyme protects against cirrhosis.
- organism: human
- assay: GWAS summary statistics
- research focus: GWAS / association mapping
- approach: statistical model
- Citations
- 160
- FWCI
- 13.76
- Field percentile
- top 1%
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