Genetic Variation Near Chrxq22 Q23 Is Linked To Emotional Functioning In Cystic Fibrosis

Cystic Fibrosis (CF) is the most common life-limiting genetic disease in the Caucasian population, diagnosed in approximately 1 in every 3,500 newborns (Cronly et al., 2018). While CF is ultimately fatal in its effect on the pulmonary and gastrointestinal (GI) systems, treatment has evolved significantly over the last 79 years. When CF was first described in 1938, the diagnosis carried with it a life expectancy of no more than a few months. By 2017, that life expectancy has skyrocketed to nearly 40 years of age, allowing individuals with CF to live much longer and more fulfilling lives. The drastic increase in life expectancy for CF patients has improved countless lives, but has also introduced new challenges to CF patients, researchers, and clinicians. One such challenge is the association of increased complications with longer survival, as well as increased risk for decreased health-related quality of life (HRQOL) (Dill, Dawson, Sellers, Robinson, & Sawicki, 2013; Havermans, Colpaert, Vanharen, & Dupont, 2009).Through genome-wide association studies (GWAS), multiple genetic regions modifying CF-related pulmonary and gastrointestinal symptoms have been identified, but their translation to clinical benefit remains elusive. Symptom variation in CF patients has been previously associated with changes in health-related quality of life (HRQOL), but the relationship between CF symptom-modifying genetic loci and HRQOL has not been explored. The purpose of this study was to determine whether two previously identified genetic modifiers of CF-related pathology also modify the subscales of HRQOL. HRQOL and genotype data were obtained and analyzed. Linear regressions were used to examine the amount of variance in HRQOL subscales that could be explained by genotype for each modifier locus. A significant regression equation was found between genotype for rs5952223, a variant near chrXq22-q23, and emotional functioning in a sample of 129 CF patients. These data suggest that genotype for this single nucleotide polymorphism (SNP) is associated with emotional functioning in CF patients and highlight this genetic region as a potential therapeutic target, irrespective of cystic fibrosis transmembrane conductance regulator (CFTR) genotype.