| Abstrakt: |
Low cardiorespiratory fitness, measured as maximal oxygen uptake (...), is associated with all-cause mortality and diseasespecific morbidity and mortality and is estimated to have a large genetic component (~60%). However, the underlying mechanisms explaining the associations are not known, and no association study has assessed shared genetics between directly measured ... and disease. We believe that identifying the mechanisms explaining how low ... is related to increased disease risk can contribute to prevention and therapy. We used a phenome-wide association study approach to test for shared genetics. A total of 64,479 participants from the Trøndelag Health Study (HUNT) were included. Genetic variants previously linked to ... were tested for association with diseases related to the cardiovascular system, diabetes, dementia, mental disorders, and cancer as well as clinical measurements and biomarkers from HUNT. In the total population, three single-nucleotide polymorphisms (SNPs) in and near the follicle-stimulating hormone receptor gene (FSHR) were found to be associated (false discovery rate < 0.05) with serum creatinine levels and one intronic SNP in the Rap-associating DIL domain gene (RADIL) with diabetes type 1 with neurological manifestations. In males, four intronic SNPs in the PBX/knotted homeobox 2 gene (PKNOX2) were found to be associated with endocarditis. None of the association tests in the female population reached overall statistical significance; the associations with the lowest P values included other cardiac conduction disorders, subdural hemorrhage, and myocarditis. The results might suggest shared genetics between ... and disease. However, further effort should be put into investigating the potential shared genetics between inborn ... and disease in larger cohorts to increase statistical power. [ABSTRACT FROM AUTHOR] |
