Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Ben Brumpton
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway; Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Bjørn Olav Åsvold
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom
Medical Research Council Integrative Epidemiology Unit, Population Health Sciences, University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
Background: Taller people have a lower risk of coronary heart disease but a higher risk of many cancers. Mendelian randomization (MR) studies in unrelated individuals (population MR) have suggested that these relationships are potentially causal. However, population MR studies are sensitive to demography (population stratification, assortative mating) and familial (indirect genetic) effects. Methods: In this study, we performed within-sibship MR analyses using 78,988 siblings, a design robust against demography and indirect genetic effects of parents. For comparison, we also applied population MR and estimated associations with measured height. Results: Within-sibship MR estimated that 1 SD taller height lowers the odds of coronary heart disease by 14% (95% CI: 3–23%) but increases the odds of cancer by 18% (95% CI: 3–34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and low-density lipoprotein cholesterol, which may mediate some of the protective effects of taller height on coronary heart disease risk. Conclusions: For the first time, we have demonstrated that the purported effects of height on adulthood disease risk are unlikely to be explained by demographic or familial factors, and so likely reflect an individual-level causal effect. Disentangling the mechanisms via which height affects disease risk may improve the understanding of the etiologies of atherosclerosis and carcinogenesis. Funding: This project was conducted by researchers at the MRC Integrative Epidemiology Unit (MC_UU_00011/1) and also supported by a Norwegian Research Council Grant number 295989.
