A non-synonymous AGER SNP (rs2070600) was associated with FEV1/FVC at genome-wide significance in our study and independently confirmed in SpiroMeta. The AGER protein, a membrane-bound or soluble pattern recognition receptor, belongs to the immunoglobulin superfamily of cell surface receptors. The SNP rs2070600 has functional significance, e.g., higher ligand affinity and production of proinflammatory proteins upon activation27. In healthy adult mice and humans, AGER is highly expressed in the lung28, and its absence contributes to the pathogenesis of idiopathic pulmonary fibrosis29,30. AGER signaling is involved in host defense, inflammation, and tissue remodeling, which are relevant processes for accelerated decline in pulmonary function with age.
