{"doi":"10.1007/s10654-023-01029-w","title":"Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    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 [\n                    <jats:italic>B</jats:italic>\n                    ] = 0.282 MET-h/wk per SD of PRS for PA, 95% confidence interval [\n                    <jats:italic>CI</jats:italic>\n                    ] = 0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier cardiometabolic profile (waist circumference [\n                    <jats:italic>B </jats:italic>\n                    = -0.003 cm, 95%\n                    <jats:italic>CI =</jats:italic>\n                    -0.004, -0.002], body mass index [\n                    <jats:italic>B </jats:italic>\n                    = -0.002 kg/m\n                    <jats:sup>2</jats:sup>\n                    , 95%\n                    <jats:italic>CI</jats:italic>\n                    = -0.004, -0.001], high-density lipoprotein cholesterol [\n                    <jats:italic>B</jats:italic>\n                     = 0.004 mmol/L, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.002, 0.006]) and lower incidence of hypertensive diseases (Hazard Ratio\n                    <jats:italic>[HR]</jats:italic>\n                     = 0.97, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.951, 0.990), stroke (\n                    <jats:italic>HR</jats:italic>\n                     = 0.94, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.903, 0.978) and type 2 diabetes (\n                    <jats:italic>HR</jats:italic>\n                     = 0.94, 95 %\n                    <jats:italic>CI</jats:italic>\n                    = 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.\n                  </jats:p>","journal":"European Journal of Epidemiology","year":2023,"id":616326,"datarank":0.40620753016533157,"base_score":2.70805020110221,"endowment":2.70805020110221,"self_citation_contribution":0.40620753016533157,"citation_network_contribution":0.0,"self_endowment_contribution":0.40620753016533157,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":570890,"name":"Timo Törmäkangas","orcid":"0000-0001-7268-5297","position":1,"is_corresponding":false},{"id":14665,"name":"Teemu Palviainen","orcid":"0000-0002-7847-8384","position":2,"is_corresponding":false},{"id":1191789,"name":"Matti Hyvärinen","orcid":"0000-0002-5086-3635","position":3,"is_corresponding":false},{"id":873766,"name":"Marie Klevjer","orcid":"0000-0001-8372-276X","position":4,"is_corresponding":false},{"id":1162164,"name":"Laura Joensuu","orcid":"0000-0002-9544-6552","position":5,"is_corresponding":false},{"id":34098,"name":"Urho M. Kujala","orcid":"0000-0002-9262-1992","position":6,"is_corresponding":false},{"id":1070,"name":"Jaakko Kaprio","orcid":"0000-0002-3716-2455","position":7,"is_corresponding":false},{"id":873768,"name":"Anja Bye","orcid":"0000-0003-1259-5542","position":8,"is_corresponding":false},{"id":304714,"name":"Elina Sillanpää","orcid":"0000-0001-6375-959X","position":9,"is_corresponding":false},{"id":1191788,"name":"Niko Paavo Tynkkynen","orcid":"0000-0001-8245-1275","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Associations of polygenic inheritance of physical activity with aerobic fitness, cardiometabolic risk factors and diseases: the HUNT study","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>\n                    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 [\n                    <jats:italic>B</jats:italic>\n                    ] = 0.282 MET-h/wk per SD of PRS for PA, 95% confidence interval [\n                    <jats:italic>CI</jats:italic>\n                    ] = 0.211, 0.354) but not with aerobic fitness. These genotypes were also associated with healthier cardiometabolic profile (waist circumference [\n                    <jats:italic>B </jats:italic>\n                    = -0.003 cm, 95%\n                    <jats:italic>CI =</jats:italic>\n                    -0.004, -0.002], body mass index [\n                    <jats:italic>B </jats:italic>\n                    = -0.002 kg/m\n                    <jats:sup>2</jats:sup>\n                    , 95%\n                    <jats:italic>CI</jats:italic>\n                    = -0.004, -0.001], high-density lipoprotein cholesterol [\n                    <jats:italic>B</jats:italic>\n                     = 0.004 mmol/L, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.002, 0.006]) and lower incidence of hypertensive diseases (Hazard Ratio\n                    <jats:italic>[HR]</jats:italic>\n                     = 0.97, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.951, 0.990), stroke (\n                    <jats:italic>HR</jats:italic>\n                     = 0.94, 95%\n                    <jats:italic>CI =</jats:italic>\n                    0.903, 0.978) and type 2 diabetes (\n                    <jats:italic>HR</jats:italic>\n                     = 0.94, 95 %\n                    <jats:italic>CI</jats:italic>\n                    = 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.\n                  </jats:p>","is_dataset_classified":null,"base_score":2.639057329615259,"endowment":2.639057329615259,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37603226","pmcid":"PMC10501929","openalex_id":"https://openalex.org/W4386019138","authors":[],"funders":[{"funder_name":"Research Council of Finland","grant_id":"346509","title":"Investigating causal interactions between physical activity and cardiometabolic disease via polygenic risk scores (GenActive)"},{"funder_name":"Research Council of Finland","grant_id":"341750","title":"Investigating causal interactions between physical activity and cardiometabolic disease via polygenic risk scores (GenActive)"},{"funder_name":"University of Jyväskylä","grant_id":"","title":null}],"total_grants":3,"fwci":2.8121,"citation_percentile":0.91254888,"influential_citations":0,"citation_trend":[{"year":2024,"count":4},{"year":2025,"count":6},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s10654-023-01029-w.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s10654-023-01029-w.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s10654-023-01029-w/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10654-023-01029-w","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37603226","host_type":"repository"},{"url":"http://urn.fi/URN:NBN:fi:jyu-202308254778","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10501929","host_type":"repository"},{"url":"https://jyx.jyu.fi/bitstreams/c9208781-9135-4ea1-bcae-0a3975b152e3/download","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10501929/pdf/10654_2023_Article_1029.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10501929","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10501929?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1101/2023.03.24.23287686","host_type":""},{"url":"http://dx.doi.org/10.1007/s10654-023-01029-w","host_type":""}],"fields_of_study":["Genetic Associations and Epidemiology","Genetics and Physical Performance","Obesity, Physical Activity, Diet","0301 basic medicine","03 medical and health sciences","Humans","Cardiometabolic Risk Factors","Diabetes Mellitus, Type 2","Exercise","Hypertension","Multifactorial Inheritance","Genetic Risk Score"],"mesh_terms":["Cardiometabolic Risk Factors","Genetic Risk Score","Diabetes Mellitus, Type 2","Humans","Hypertension","Exercise","Multifactorial Inheritance"],"keywords":["Medicine","Hazard ratio","Body mass index","Aerobic exercise","Physical fitness","Internal medicine","Confidence interval","Waist","Proportional hazards model","Type 2 diabetes","VO2 max","Genotype","Diabetes mellitus","Blood pressure","Endocrinology","Physical therapy","Genetics","Heart rate","Biology","Common Disease","Physical Activity","Health Behaviour","Gene-environment Interaction","Polygenic Risk Score","Multifactorial Inheritance","Hyvinvoinnin tutkimuksen yhteisö","Humans","Sports and Exercise Medicine","Exercise","perinnöllisyys","Genetic Risk Score","School of Wellbeing","Gerontologia ja kansanterveys","Cardiometabolic Risk Factors","riskitekijät","Liikuntalääketiede","fyysinen kunto","Diabetes Mellitus, Type 2","Genetic Epidemiology","Hypertension","sydän- ja verisuonitaudit","geneettiset tekijät","Gerontology and Public Health","fyysinen aktiivisuus"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T22:34:47.234621Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}