Here, we confirmed that individuals homozygous and heterozygous for AATD risk alleles both have increased rates of liver transplantation, demonstrated that there is a gene-environment interaction between AATD-risk alleles and hepatitis C infection in the context of need for liver transplantation, and identified individuals who are compound heterozygous for rare pathogenic variants in SERPINA1 whose symptoms overlap with AATD but lack a formal diagnosis, at times despite having been clinically tested. Here, SERPINA1 is linked to alpha 1-antitrypsin deficiency.