ArticleExperimental gerontology2018
Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study.
Article in Experimental gerontology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Systematic review of Mendelian randomization studies on risk of cancer.BMC medicine · 2022Pooled it
- Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.Nature communications · 2020Pooled it
- The causal role of genetically predicted obesity-related traits in heart failure: systematic review and meta-analysis of Mendelian randomization studies.Frontiers in cardiovascular medicine · 2026Review
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.Molecular biology reports · 2024Article
- Article
- Semiparametric regression analysis of bivariate censored events in a family study of Alzheimer's disease.Biostatistics (Oxford, England) · 2022Article
- Statistical methods for Mendelian randomization in genome-wide association studies: A review.Computational and structural biotechnology journal · 2022Review
- Data-driven identification of ageing-related diseases from electronic health records.Scientific reports · 2021Article
- Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer.International journal of cancer · 2021Article
- Higher BMI is linked to an increased risk of heart attacks in European adults: a Mendelian randomisation study.BMC cardiovascular disorders · 2020Article
- Genetics Insights in the Relationship Between Type 2 Diabetes and Coronary Heart Disease.Circulation research · 2020Review
- Serum albumin and atrial fibrillation: insights from epidemiological and mendelian randomization studies.European journal of epidemiology · 2020Article
- How Genomics Is Personalizing the Management of Dyslipidemia and Cardiovascular Disease Prevention.Current cardiology reports · 2018Review
- Mendelian randomization studies of cancer risk: a literature review.Current epidemiology reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundsElucidating the causal effects of common intermediate risk factors on the onset of age-related diseases is indispensable for developing prevention and intervention procedures.
methodsWe conducted two-stage time-to-event Mendelian randomization meta-analyses combining five large-scale longitudinal cohorts to investigate dynamic causal effects of cardiovascular disease risk factors including body mass index (BMI), systolic blood pressure (SBP), and lipids on the age-at-onset of age-related diseases. We constructed weighted polygenic scores based on genetic markers from previously reported genome-wide association studies as instrumental variables to estimate the causal effects. To avoid false positive due to potential pleiotropic effects of the genetic markers, we performed a leave-one-out sensitivity analysis and an MR-Egger sensitivity analysis that we expanded in the survival context.
resultsOur results show that elevated BMI increases the absolute risk of type 2 diabetes (T2D) (p=7.68e-04), heart failure (p=9.03e-03), and cardiovascular diseases (CVD) (p=1.69e-03) and the causal effects start at different ages. A significant association between BMI and the risk of stroke is observed; however, the sensitivity analyses suggest that the association is attributed to the potential pleiotropic effects of rs2867125 and rs1558902. Raised SBP levels are significantly associated with the development of atrial fibrillation (p=6.42e-03). Low-density lipoprotein cholesterol (LDL-C) levels are inversely associated with the age-at-onset of T2D (p=1.05e-02). In addition, LDL-C and triglycerides are inversely associated with the risks of cancer and T2D, respectively. Nevertheless, the sensitivity analyses suggest that these associations are probably due to pleiotropic effects of several single-nucleotide polymorphisms including rs4970834 and rs1260326.
conclusionsOur results highlight the involvement of BMI in the development of multiple age-related diseases. Some observed causal associations can attribute to pleiotropic effects of some genetic variations. These findings have important implications in unraveling causal effects of common risk factors on age-related diseases and guiding effective intervention strategies to reduce the incidence of these diseases.
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