Epidemiology and Genetics of Preserved Ratio Impaired SpiroMetry (PRISm): An Analysis of UK Biobank

RationalePreserved ratio impaired spirometry (PRISm) is defined as Forced Expiratory Volume in one second 0.70. It may be a precursor of COPD and has been associated with increased respiratory symptoms and comorbidities. Current understanding of PRISm is based on small selective cohorts and genetic determinants remain unknown. ObjectivesIdentify the prevalence, risk factors, co-morbidity, and genetics of PRISm in a large cohort to improve power and generalizability. MethodsThe UKBiobank, provides a large cohort of genotyped individuals. Regression analysis determined risk factors for and associated co-morbidities of PRISm. Genome wide association studies, conditional, and gene-based analyses were performed with a PheWAS and literature search conducted on the results. Measurements and Main ResultsPRISm has a similar prevalence to airflow obstruction (8% vs 7.8%) and is associated with increased cardiovascular co-morbidity, OR of 1.26 (95%CI 1.20-1.31) after adjusting for BMI, smoking status, age, diabetes, and sex. Genetic analysis discovered four associated single nucleotide polymorphisms and eight genes. Two SNPs have not been described with respiratory disease before. Other genetic loci identified are known to increase risk of asthma and COPD, and influence response to inhaled steroids. ConclusionsPRISm affects 8% of adults of whom [~]40% report cardiovascular comorbidity. Detailed analysis reveals that PRISm has shared genetic associations with asthma and COPD. These findings highlight the need for research into the potential therapeutic strategies and screening for individuals with PRISm, in particular whether this may reduce transition to COPD and reduce cardiovascular disease.