Trade-offs in aging lung diseases: a review on shared but opposite genetic risk variants in idiopathic pulmonary fibrosis, lung cancer and chronic obstructive pulmonary disease

PURPOSE OF REVIEW: The process of aging involves biological changes that increases susceptibility for disease. In the aging lung disease IPF, GWAS studies identified genes associated with risk for disease. Recently, several of these genes were also found to be involved in risk for COPD or lung cancer. This review describes GWAS-derived risk genes for IPF that overlap with risk genes for lung cancer or COPD. RECENT FINDINGS: Risk genes that overlap between aging lung diseases, include FAM13A, DSP and TERT. Most interestingly, disease predisposing alleles for IPF are opposite to those for COPD or lung cancer. Studies show that the alleles are associated with differential gene expression and with physiological traits in the general population. The opposite allelic effect sizes suggest the presence of trade-offs in the aging lung. For TERT, the trade-off involves cellular senescence versus proliferation and repair. For FAM13A and DSP, trade-offs may involve protection from noxious gases or tissue integrity. SUMMARY: The overlap in risk genes in aging lung diseases provides evidence that processes associated with FAM13A, DSP and TERT are important for healthy aging. The opposite effect size of the disease risk alleles may represent trade-offs, for which a model involving an apicobasal gene expression gradient is presented.