A gene-based analysis of rare, nonsynonymous <i>ADRB2</i> variants, identified a novel association with nonrheumatic pulmonary valve disorders, but no association with lung function.<h4>Discussion</h4>In conclusion, the lung function-lowering allele of Thr164Ile is associated with traits and proteins indicative of a role in immune and lipid metabolism pathways, suggesting potential targets for therapeutic intervention. The gene discussed is ADRB2; the disease is pulmonary valve disorder.