Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study

• Published in: European journal of epidemiology 2023-09, Vol.38 (9), p.995-1008
• Main Authors: Tynkkynen, Niko Paavo, Törmäkangas, Timo, Palviainen, Teemu, Hyvärinen, Matti, Klevjer, Marie, Joensuu, Laura, Kujala, Urho, Kaprio, Jaakko, Bye, Anja, Sillanpää, Elina
• Format: Article
• Language: English
• Subjects: Body mass index; Body measurements; Body size; Cardiology; Cardiometabolic Risk Factors; Cardiorespiratory fitness; Cholesterol; Confidence intervals; Continuity (mathematics); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2; Epidemiology; Exercise; Gene polymorphism; Genetic Epidemiology; Genetic factors; Genetic Risk Score; Genotypes; Health risks; High density lipoprotein; Humans; Hypertension; Infectious Diseases; Medicine; Medicine & Public Health; Multifactorial Inheritance; Nucleotides; Oncology; Phenotypes; Physical activity; Physical fitness; Polygenic inheritance; Polymorphism; Public Health; Regression analysis; Regression models; Risk factors; Self report; Single-nucleotide polymorphism; Statistical analysis; Statistical models
• ISSN: 0393-2990; 1573-7284; 1573-7284
• DOI: 10.1007/s10654-023-01029-w

Physical activity (PA), aerobic fitness, and cardiometabolic diseases (CMD) are highly heritable multifactorial phenotypes. Shared genetic factors may underlie the associations between higher levels of PA and better aerobic fitness and a lower risk for CMDs. We aimed to study how PA genotype associates with self-reported PA, aerobic fitness, cardiometabolic risk factors and diseases. PA genotype, which combined variation in over one million of gene variants, was composed using the SBayesR polygenic scoring methodology. First, we constructed a polygenic risk score for PA in the Trøndelag Health Study (N = 47,148) using UK Biobank single nucleotide polymorphism-specific weights (N = 400,124). The associations of the PA PRS and continuous variables were analysed using linear regression models and with CMD incidences using Cox proportional hazard models. The results showed that genotypes predisposing to higher amount of PA were associated with greater self-reported PA (Beta [ B ] = 0.282 MET-h/wk per SD of PRS for PA, 95% confidence interval [ CI ] = 0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier cardiometabolic profile (waist circumference [ B  = -0.003 cm, 95% CI = -0.004, -0.002], body mass index [ B  = -0.002 kg/m 2 , 95% CI = -0.004, -0.001], high-density lipoprotein cholesterol [ B  = 0.004 mmol/L, 95% CI = 0.002, 0.006]) and lower incidence of hypertensive diseases (Hazard Ratio [HR]  = 0.97, 95% CI = 0.951, 0.990), stroke ( HR  = 0.94, 95% CI = 0.903, 0.978) and type 2 diabetes ( HR  = 0.94, 95 % CI = 0.902, 0.970). Observed associations were independent of self-reported PA. These results support earlier findings suggesting small pleiotropic effects between PA and CMDs and provide new evidence about associations of polygenic inheritance of PA and intermediate cardiometabolic risk factors.