The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD
Hepatol Commun. 2022 Mar 15. doi: 10.1002/hep4.1932. Online ahead of print.
Theresia M Schnurr12, Sophia Figueroa Katz13, Johanne M Justesen12, Jack W O'Sullivan1, Peter Saliba-Gustafsson14, Themistocles L Assimes15, Ivan Carcamo-Orive16, Aijaz Ahmed7, Euan A Ashley189, Torben Hansen2, Joshua W Knowles1610
Author information
Department of Medicine, Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, California, USA.
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Kobenhavn, Denmark.
Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA.
Cardiovascular Medicine Unit, Department of Medicine, Center for Molecular Medicine at BioClinicum, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
VA Palo Alto Health Care System, Palo Alto, California, USA.
Stanford Diabetes Research Center, Stanford, California, USA.
Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA.
Department of Genetics, Stanford University, Stanford, California, USA.
Department of Biomedical Data Science, Stanford University, Stanford, California, USA.
Stanford Prevention Research Center, Stanford, California, USA.
Abstract
Genetic predisposition and unhealthy lifestyle are risk factors for nonalcoholic fatty liver disease (NAFLD). We investigated whether the genetic risk of NAFLD is modified by physical activity, muscular fitness, and/or adiposity. In up to 242,524 UK Biobank participants without excessive alcohol intake or known liver disease, we examined cross-sectional interactions and joint associations of physical activity, muscular fitness, body mass index (BMI), and a genetic risk score (GRS) with alanine aminotransferase (ALT) levels and the proxy definition for suspected NAFLD of ALT levels > 30 U/L in women and >40 U/L in men. Genetic predisposition to NAFLD was quantified using a GRS consisting of 68 loci known to be associated with chronically elevated ALT. Physical activity was assessed using accelerometry, and muscular fitness was estimated by measuring handgrip strength. We found that increased physical activity and grip strength modestly attenuate genetic predisposition to elevation in ALT levels, whereas higher BMI markedly amplifies it (all p values < 0.001). Among those with normal weight and high level of physical activity, the odds of suspected NAFLD were 1.6-fold higher in those with high versus low genetic risk (reference group). In those with high genetic risk, the odds of suspected NAFLD were 12-fold higher in obese participants with low physical activity versus those with normal weight and high physical activity (odds ratio for NAFLD = 19.2 and 1.6, respectively, vs. reference group). Conclusion: In individuals with high genetic predisposition for NAFLD, maintaining a normal body weight and increased physical activity may reduce the risk of NAFLD.