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Exploring shared genetics between maximal oxygen uptake and disease: the HUNT study.

Ada N Nordeidet1, Marie Klevjer1,2, Ulrik Wisløff1,3

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Physiological Genomics
|August 14, 2023
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Summary

Low cardiorespiratory fitness (CRF) has a genetic basis and may share genetic links with diseases like diabetes and endocarditis. This study identified potential genetic associations between CRF and specific health conditions, suggesting shared genetic mechanisms.

Keywords:
HUNTfitnessgenetic pleiotropygenetic variationoxygen uptake

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Area of Science:

  • Genetics
  • Cardiovascular Health
  • Metabolic Disorders

Background:

  • Low cardiorespiratory fitness (CRF), measured by maximal oxygen uptake (V̇o2max), is linked to increased mortality and morbidity.
  • Approximately 60% of CRF variation is attributed to genetic factors, but the underlying mechanisms connecting CRF to disease risk remain unclear.
  • No prior studies have investigated shared genetics between directly measured CRF and specific diseases.

Purpose of the Study:

  • To explore shared genetic underpinnings between cardiorespiratory fitness and various diseases using a phenome-wide association study (PheWAS) approach.
  • To identify genetic variants associated with V̇o2max that also correlate with disease risk, clinical measurements, and biomarkers.
  • To elucidate potential mechanisms linking low CRF to elevated disease risk for improved prevention and therapy.

Main Methods:

  • Utilized data from 64,479 participants in the Trøndelag Health Study (HUNT).
  • Employed a phenome-wide association study (PheWAS) design to test genetic variants previously associated with V̇o2max against a wide range of diseases and clinical traits.
  • Analyzed associations with cardiovascular diseases, diabetes, dementia, mental disorders, cancer, and various biomarkers.

Main Results:

  • Identified significant associations between specific SNPs near the *FSHR* gene and serum creatinine levels (in the total population).
  • Found an association between an intronic SNP in the *RADIL* gene and type 1 diabetes with neurological manifestations.
  • Observed associations between *PKNOX2* gene SNPs and endocarditis in males; no significant associations were found in females, though trends included cardiac conduction disorders and subdural hemorrhage.

Conclusions:

  • The study suggests potential shared genetic factors between cardiorespiratory fitness and specific diseases, including serum creatinine levels, diabetes, and endocarditis.
  • Findings indicate that genetic variants influencing CRF may also impact disease susceptibility.
  • Further research in larger cohorts is recommended to confirm these genetic associations and increase statistical power.