Background

Both high fitness and a low resting heart rate are closely linked to good health. We have found several genes that are directly related to fitnes level, whereas the genes that affect resting heart rate are not particularly well mapped today. In her doctoral work, Ada Nilsen Nordeidet is looking for new resting heart rate genes and at the same time trying to map the mechanisms that make these genes so important for the resting heart rate. She also looks at how both fitness and resting heart rate genes are connected to other factors that affect our health. In her work, she uses both data from the Nord-Trøndelag Health Study and from a large British database.

High fitness is associated with good heart health. We do not know to what extent genes contribute to this association. In the last article in her doctorate, Ada investigates whether overproduction of one specific fitness gene can make heart muscle cells work better. We either increase or decrease the genetic expression of this fitness gene in heart muscle cells that have been obtained from humans, and then investigate how this affects the function of the cells.

Genes that are linked to high fitness can also be linked to other things that affect our health. For example, our findings suggest that fitness genes also have an effect on the levels of creatinine in the blood and the risk of developing type 1 diabetes. We also found less certain signs that good fitness genes can lead to lower BMI, healthier levels of HDL cholesterol and lower resting heart rate.

We previously published the world's largest analysis of gene variants associated with directly measured fitness. In the new study, we investigated whether the 22 gene variants that were most closely linked to maximum oxygen uptake in that study are also linked to other measures of health. 65,000 participants from the second and third round of the Nord-Trøndelag Health Study have contributed data to the analyses. In addition to data from the health survey itself, we have also obtained information about hospital-registered diagnoses for the same people between 1999 and 2017.

Three of the gene variants that are linked to good fitness could also be linked to increased levels of creatinine in the blood. Increased levels of creatinine are associated with increased muscle mass. We can speculate that these three gene variants have an effect on muscle mass and in that way both give increased levels of creatinine and higher VO2 max. We checked the findings by doing the same analyses in a large British database, and found that two of the same gene variants were linked to increased creatinine levels. The analyzes from HUNT further indicate that a gene variant that increases fitness can significantly increase the risk of type 1 diabetes with neurological manifestations.

When we examined 33 gene variants that are only associated with fitness in men, we found that four of them are also linked to a significantly increased risk of endocarditis, an inflammatory disease of the inside of the heart. It is not unusual for genes linked to good health in one area to be bad for health in one or more other areas. For women, we found no reliable relationships between 44 gene variants and other health variables.

Although we did not find many reliable connections, we did make several interesting findings that have lower statistical power. Among other things, we saw signs that some of the genes that can give high fitness can also give a lower BMI for both sexes and healthier levels of HDL cholesterol and a lower resting heart rate for women.

Read the full research article in Physiological Genomics:
Exploring shared genetics between maximal oxygen uptake and disease: the HUNT study

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