SERPINA1 and alpha 1-antitrypsin deficiency: The next strongest effect on either enzyme was rs28929474, a missense variant (the Pi-Z allele) in SERPINA1 (serpin family A member 1) which causes alpha-1 antitrypsin deficiency (AATD) in its homozygous state35, associated with a 2.5% increase in ALT (95% CI, 2.1% to 2.8%; p = 1.4 × 10−72) and 1.3% increase in AST (95% CI, 1.1% to 1.5%; p = 3.2 × 10−50); AATD manifests with both lung and liver damage.