ABSTRACT
To elucidate the host genetic loci affecting severity of SARS-CoV-2 infection, or Coronavirus disease 2019 (COVID-19), is an emerging issue in the face of the current devastating pandemic. Here, we report a genome-wide association study (GWAS) of COVID-19 in a Japanese population led by the Japan COVID-19 Task Force, as one of the initial discovery GWAS studies performed on a non-European population. Enrolling a total of 2,393 cases and 3,289 controls, we not only replicated previously reported COVID-19 risk variants (e.g., LZTFL1, FOXP4, ABO, and IFNAR2), but also found a variant on 5q35 (rs60200309-A at DOCK2) that was associated with severe COVID-19 in younger (<65 years of age) patients with a genome-wide significant p-value of 1.2 x 10-8 (odds ratio = 2.01, 95% confidence interval = 1.58-2.55). This risk allele was prevalent in East Asians, including Japanese (minor allele frequency [MAF] = 0.097), but rarely found in Europeans. Cross-population Mendelian randomization analysis made a causal inference of a number of complex human traits on COVID-19. In particular, obesity had a significant impact on severe COVID-19. The presence of the population-specific risk allele underscores the need of non-European studies of COVID-19 host genetics.
ABSTRACT
To investigate the influence of long-distance running on bone metabolism, we measured bone metabolism markers in eight healthy young men before and 4 months after the start of training program of 10 km running. Measurements were then taken the day before a marathon race, immediately after, and 1 day, 2 days and 5 days after.<BR>As a result of exercise, the levels of serum osteocalcin (OC), a bone formation marker, and urinary deoxypyridinolin (D-Pyr), a bone resorption marker, decreased significantly. After the marathon race, the OC level decreased further corresponding to an increase of hydrocortisone right after the race. However, from the day following the race, the OC level showed a slight increase. D-Pyr showed an increasing tendency immediately after the race, and the levels of OC and D-Pyr increased significantly 5 days after the race.<BR>Bone formation and resorption decreased as a result of light, low-frequency endurance exercise. However, both of them increased after intense physical stress. From this result, it is suggested that the intensity and frequency of exercise affect bone metabolism differently, even though the type of exercise load is similar.