PR98420

REYKJAVIK, Iceland Oct 24th, 2022 /PRNewswire=KYODO JBN/

Scientists at deCODE genetics, a subsidiary of Amgen, publish today a large

genome-wide association study on nonalcoholic fatty liver disease (NAFLD) in

Nature Genetics.

Sequence variants that associate with NAFLD were identified, including rare,

protective loss-of-function variants that point to potential drug targets.

Plasma proteomic analyses provided further insight into the pathogenesis of

NAFLD

NAFLD is a growing health problem and is estimated to affect up to 25% of the

world's population. Nonalcoholic fatty liver (NAFL), when over 5% of the liver

is fat with no identifiable causes such as excessive alcohol consumption, is

the first stage of NAFLD. NAFL can progress to non-alcoholic steato-hepatitis

(NASH) which can progress further into liver cirrhosis and hepatocellular

carcinoma (HCC). NAFLD can be difficult to diagnose and monitor and there is

currently no therapy available. The identification of potential drug targets

and biomarkers is therefore of great importance.

A large genome-wide association study of NAFL, liver cirrhosis and HCC was

conducted and the findings integrated with expression and proteomic data. For

NAFL, 9,491 clinical cases from Iceland, UK, USA and Finland were utilized in

addition to proton density fat fraction (PDFF) extracted from 36,116 liver

MRIs. Among the sequence variants the scientists found, in the Icelandic

population,were rare, protective, predicted loss-of-function variants in MTARC1

and GPAM suggesting that inhibiting MTARC1 or GPAM could be therapeutic for

NAFL or NASH.

Levels of thousands of proteins measured in plasma were analyzed, identifying

potential biomarkers of disease, disease progression or target engagement and

models that can discriminate between a NAFL and cirrhosis were constructed

using the proteomics data. The results therefore provide a path to  the

development of non-invasive tools to evaluate and diagnose NAFLD.

Additionally, the pleiotropic effects of the identified variants were explored

by looking at associations with 52 other phenotypes and traits. BMI is one of

the most common risk factors of NAFLD and longitudinal PDFF measures suggested

that carriers of p.Ile148Met, the well-know NAFLD risk variant, in PNPLA3 are

more susceptible to change in BMI than non-carriers.

To date this study is one of the largest ones conducted to shed light on the

genetic basis of NAFLD and the results will hopefully contribute to the

development of diagnostic tools or therapies that can help patients suffering

from NAFLD.

CONTACT:

Thora Kristin Asgeirsdottir,

thoraa@decode.is

+354 894 1909

deCODE genetics

Photo - https://mma.prnewswire.com/media/1926826/deCODE_genetics.jpg

Source: deCODE genetics