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

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.