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Disclosures: Marco De Giorgi: Nothing to Disclose, So Hyun Park: Nothing to Disclose, Adam Castoreno: Nothing to Disclose, Mingming Cao: Nothing to Disclose, Ayrea Hurley: Nothing to Disclose, Lavanya Saxena: Nothing to Disclose, Marcel Chuecos: Nothing to Disclose, Christopher Walkey: Nothing to Disclose, Alexandria Doerfler: Nothing to Disclose, Mia Furgurson: Nothing to Disclose, Cecilia Ljungberg: Nothing to Disclose, Kalyani Patel: Nothing to Disclose, Sarah Hyde: Nothing to Disclose, Tyler Chickering: Nothing to Disclose, Stephanie Lefebvre: Nothing to Disclose, Kelly Wassarman: Nothing to Disclose, Patrick Miller: Nothing to Disclose, June Qin: Nothing to Disclose, Mark Schlegel: Alnylam Pharmaceuticals: Employee, Ivan Zlatev: Nothing to Disclose, Rich Gang Li: Nothing to Disclose, Jong Kim: Nothing to Disclose, James Martin: Nothing to Disclose, Karl-Dimiter Bissig: Nothing to Disclose, Vasant Jadhav: Nothing to Disclose, Gang Bao: Nothing to Disclose, William Lagor: Alnylam Pharmaceuticals: Receive research reagents as part of a collaboration 2552 HIGH INHERITED RISK BY POLYGENIC SCORE MORE THAN DOUBLES AGE-ASSOCIATED INCREASES IN FIBROSIS IN MID-LIFE IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) Veeral Ajmera 1 Kaleb Tesfai 2 Saaket Agrawal 3 Amit Khera 4 Rohit Loomba 1 , 1 University of California, San Diego, 2 UCSD MASLD Research Center, 3 Broad Institute, 4 Verve Therapeutics Background: Despite longstanding knowledge of the importance of certain genetic variants as key drivers of risk for MASLD, they have not been incorporated into clinical practice due to limited granular data on their impact in cohorts with advanced continuous biomarkers of disease severity