| Application: | 15031, Genetic dissection of cardiovascular risk factors and their relation to disease to establish causality and identify novel targets of therapy |
| Title: | Genetic study links components of the autonomous nervous system to heart-rate profile during exercise |
| Size: | 459120 B |
| Archived: | 24 Nov 2020 |
| Stability: | Complete |
| Personal: | No individual-level data |
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Notes
Heart rate (HR) responds to exercise by increasing during exercise and recovering after exercise. As such, HR is an important predictor of mortality that researchers believe is modulated by the autonomic nervous system. However, the mechanistic basis underlying inter-individual differences has yet to be explained.Here, we perform a large-scale genome-wide analysis of HR increase and HR recovery in 58,818 UK Biobank individuals. Twenty-five independent SNPs in 23 loci are identified to be associated (p?<?8.3? ?10-9) with HR increase or HR recovery. A total of 36 candidate causal genes are prioritized that are enriched for pathways related to neuron biology. No evidence is found of a causal relationship with mortality or cardiovascular diseases. However, a nominal association with parental lifespan requires further study. In conclusion, the findings provide new biological and clinical insight into the mechanistic underpinnings of HR response to exercise. The results also underscore the role of the autonomous nervous system in HR recovery.
Application 15031
Genetic dissection of cardiovascular risk factors and their relation to disease to establish causality and identify novel targets of therapy
Cardiovascular disease is a major health burden and one of the main causes of premature death and disability in industrialized countries. How genetic variants act and potentially modify relationships between risk-factors and cardiovascular disease remains largely unknown. The aim of this study is to explore new insights into the causality of cardiovascular risk factors, how genetic variants might act and potentially modify relationships between risk-factors and disease. Ultimately, we aim to identify targets of therapy. The purpose of UK Biobank is to build a major resource supporting a diverse range of research intended to improve the prevention, diagnosis and treatment of illness and the promotion of health throughout society. This proposal may lead to the identification of new insights into the mechanisms how genetic variants act and potentially modify relationships between risk-factors. This in addition, would give us the opportunity to identify new therapeutic targets. We will describe the baseline parameters, history, prevalence and incidence of single and combined risk factors e.g. anthropomorphics, smoking, hypertension (blood pressure), diabetes, heart rate, renal dysfunction, (lipid/biomarker profiles and telomere length when these become available), electrolytes and lifestyle factors. We will determine their environmental and genome wide correlates and relate them to the existence of cardiovascular disease entities (coronary artery disease, heart failure, arrhythmia?s, sudden death, WHO definition of CVD), mortality and disease-free longevity in order to study the potentially causal relationships (under Mendelian assumptions) between the risk factors, mortality, co-morbidities and hospitalization. All subjects of whom the baseline parameters and history follow-up data (hospital and death reports) and genetic are available will be included (full cohort).
| Lead investigator: | Professor Pim van der Harst |
| Lead institution: | University Medical Center Groningen |
1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 2858 | Genetic study links components of the autonomous nervous system to heart-rate profile during exercise | Niek Verweij (+2) | 2018 | Nature Communications |
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