Taller height and risk of coronary heart disease and cancer, a within-sibship Mendelian randomization study
- University of Bristol, United Kingdom
- Norwegian University of Science and Technology, Norway
Abstract
Background: Taller people have lower risk of coronary heart disease but 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 Mendelian randomization estimated that one SD taller height lowers odds of coronary heart disease by 14% (95% CI: 3% to 23%) but increases odds of cancer by 18% (95% CI: 3% to 34%), highly consistent with population MR and height-disease association estimates. There was some evidence that taller height reduces systolic blood pressure and LDL cholesterol, which may mediate some of the protective effect of taller height on coronary heart disease risk.
Conclusions: For the first time, we have demonstrated that 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 understanding of the aetiologies 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.
Data availability
We used individual level data from the UK Biobank and HUNT cohorts. Participants in these studies have consented to the use of their data in medical research and so these data are not publicly available. Data access can be applied for by qualified researchers.For access to UK Biobank individual level participant data, please send enquiries to access@ukbiobank.ac.uk and see information on the UK Biobank website http://www.ukbiobank.ac.uk. UK Biobank access generally involves submitting project proposals which are evaluated by the study data access committee.Researchers associated with Norwegian research institutes can apply for the use of HUNT data and samples with approval by the Regional Committee for Medical and Health Research Ethics. HUNT data is governed by Norwegian law, therefore researchers from other countries may apply if collaborating with a Norwegian Principal Investigator. Detailed information on the data access procedure of HUNT can be found at https://www.ntnu.edu/hunt/data.Statistical code for population and within-sibship models used in the manuscript is available on GitHub https://github.com/LaurenceHowe/WithinSibshipModels/
Article and author information
Author details
George Davey Smith
Neil Martin Davies
Funding
Norwegian Research Council (295989)
- Neil Martin Davies
Medical Research Council (00011/1)
- George Davey Smith
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: This research has been conducted using the UK Biobank Resource under Application Number 15825. UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee (MREC). All UK Biobank participants provided written informed consent. The use of HUNT data in this study was approved by the Regional Committee for Ethics in Medical Research, Central Norway (2017/2479). All HUNT study participants provided written informed consent.
Copyright
© 2022, Howe et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Taller height and risk of coronary heart disease and cancer, a within-sibship Mendelian randomization study
eLife 11:e72984.
https://doi.org/10.7554/eLife.72984
Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background:
In many settings, a large fraction of the population has both been vaccinated against and infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.
Methods:
We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April–May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHRs).
Results:
275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April–May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79–0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76–0.93), 0.87 (0.83–0.90), and 0.96 (0.74–1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44–0.58) and 0.67 (0.61–0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.
Conclusions:
In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
Funding:
This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).
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- Epidemiology and Global Health
Background:
The role of circulating metabolites on child development is understudied. We investigated associations between children’s serum metabolome and early childhood development (ECD).
Methods:
Untargeted metabolomics was performed on serum samples of 5004 children aged 6–59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children’s milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥1. The interaction between significant metabolites and the child’s age was tested.
Results:
Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child’s nutritional status, diet quality, and infant age. Cresol sulfate (β=–0.07; adjusted-p <0.001), hippuric acid (β=–0.06; adjusted-p <0.001), phenylacetylglutamine (β=–0.06; adjusted-p <0.001), and trimethylamine-N-oxide (β=–0.05; adjusted-p=0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged –1 SD: β=–0.05; pP=0.01;+1 SD: β=0.05; p=0.02) and methylhistidine (–1 SD: β = - 0.04; p=0.04;+1 SD: β=0.04; p=0.03).
Conclusions:
Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding:
Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
