低心肺功能,测量为最大摄氧量(VO2max),与全因死亡率和疾病特异性发病率和死亡率相关,估计具有很大的遗传成分(约60%)。然而,解释这些关联的潜在机制是未知的,并且没有关联研究评估直接测量的VO2max和疾病之间的共有遗传学。我们假设确定解释低VO2max与疾病风险增加相关的机制可以有助于预防和治疗。我们使用了全表型关联研究(PheWAS)方法来测试共享遗传学。包括来自Trøndelag健康研究(HUNT)的64479名参与者。检测发现与VO2max相关的遗传变异与心血管系统相关疾病的相关性。糖尿病,痴呆症,精神障碍,癌症,以及HUNT的临床测量和生物标志物。在总人口中,发现FSHR及其附近的三个单核苷酸多态性(SNP)与血清肌酐水平相关(错误发现率(FDR)<0.05),和一个内含子SNP在RADIL与1型糖尿病神经表现。在男性中,发现PKNOX2中的4个内含子SNP与心内膜炎相关.女性人群中的关联测试均未达到总体统计意义,与最低p值的关联包括其他心脏传导障碍,硬膜下出血,和心肌炎.结果可能表明VO2max和疾病之间有共同的遗传学。然而,在更大的队列中,应进一步努力调查先天性VO2max与疾病之间的潜在共有遗传学,以提高统计学功效.
Low cardiorespiratory fitness, measured as maximal oxygen uptake (V̇o2max), is associated with all-cause mortality and disease-specific 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 V̇o2max and disease. We believe that identifying the mechanisms explaining how low V̇o2max 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 V̇o2max 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 V̇o2max and disease. However, further effort should be put into investigating the potential shared genetics between inborn V̇o2max and disease in larger cohorts to increase statistical power.NEW & NOTEWORTHY To our knowledge, this is the first genetic association
study exploring how genes linked to cardiorespiratory fitness (CRF) relate to disease risk. By investigating shared genetics, we found indications that genetic variants linked to directly measured CRF also affect the level of blood creatinine, risk of diabetes, and endocarditis. Less certain findings showed that genetic variants of high CRF might cause lower body mass index, healthier HDL cholesterol, and lower resting heart rate.