AATD are particularly prone to adverse outcomes from smoking and alcohol intake given they are predisposed to both lung and liver disease; this is due to the toxic loss of function of AAT in the lung (causing emphysema) and the toxic gain of function of AAT in the liver (misfolded protein causing liver injury) (Attaway et al., 2019; Stoller, 2024). This evidence concerns the gene SERPINA1 and pulmonary emphysema.