10.1016/j.exger.2017.09.019

10.1016/j.exger.2017.09.019 Experimental Gerontology 107 (2018) 74–86 Contents lists available at ScienceDirect Experimental Gerontology journal homepage: www.elsevier.com/locate/expgero Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study Liang He , Irina Culminskaya, Yury Loika, Konstantin G. Arbeev, Olivia Bagley, Matt Duan, Anatoliy I. Yashin, Alexander M. Kulminski Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27708, USA ARTICLE I NFO ABSTRACT Keywords: Backgrounds: Elucidating the causal effects of common intermediate risk factors on the onset of age-related Mendelian randomization diseases is indispensable for developing prevention and intervention procedures. Body mass index Methods: We conducted two-stage time-to-event Mendelian randomization meta-analyses combining five large- Causal effect scale longitudinal cohorts to investigate dynamic causal effects of cardiovascular disease risk factors including Age-related disease body mass index (BMI), systolic blood pressure (SBP), and lipids on the age-at-onset of age-related diseases. We Time-to-event analysis constructed weighted polygenic scores based on genetic markers from previously reported genome-wide asso- ciation 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png

10.1016/j.exger.2017.09.019

Elsevier — Jun 11, 2020

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Abstract

Experimental Gerontology 107 (2018) 74–86 Contents lists available at ScienceDirect Experimental Gerontology journal homepage: www.elsevier.com/locate/expgero Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study Liang He , Irina Culminskaya, Yury Loika, Konstantin G. Arbeev, Olivia Bagley, Matt Duan, Anatoliy I. Yashin, Alexander M. Kulminski Biodemography of Aging Research Unit, Social Science Research Institute, Duke University, Durham, NC 27708, USA ARTICLE I NFO ABSTRACT Keywords: Backgrounds: Elucidating the causal effects of common intermediate risk factors on the onset of age-related Mendelian randomization diseases is indispensable for developing prevention and intervention procedures. Body mass index Methods: We conducted two-stage time-to-event Mendelian randomization meta-analyses combining five large- Causal effect scale longitudinal cohorts to investigate dynamic causal effects of cardiovascular disease risk factors including Age-related disease body mass index (BMI), systolic blood pressure (SBP), and lipids on the age-at-onset of age-related diseases. We Time-to-event analysis constructed weighted polygenic scores based on genetic markers from previously reported genome-wide asso- ciation 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

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