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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/479| Can the impact of childhood adiposity on disease risk be reversed? A Mendelian randomization study | |
| Eleanor Sanderson Benjamin Elsworth Kate Tilling George Davey Smith Tom G Richardson | |
| Novel Coronavirus | |
| Acceso Abierto | |
| Atribución | |
| 10.1101/19008011 | |
| Objective: To evaluate whether early life adiposity has an independent effect on later life disease risk or whether its influence is mediated by adulthood body mass index (BMI). Design: Two-sample univariable and multivariable Mendelian randomization. Setting: The UK Biobank (UKB) prospective cohort study and four large-scale genome-wide association study (GWAS) consortia. Participants: 453,169 participants enrolled in the UKB and a combined total of over 700,000 individuals from different GWAS consortia. Exposures: Measured BMI during adulthood (mean age: 56.5) and self-reported adiposity at age 10. Main outcome measures: Coronary artery disease (CAD), type 2 diabetes (T2D), breast cancer and prostate cancer. Results: Individuals with genetically predicted higher BMI in early life had increased odds of CAD (OR:1.49, 95% CI:1.33-1.68) and T2D (OR:2.32, 95% CI:1.76-3.05) based on univariable MR (UVMR) analyses. However, there was little evidence of a direct effect (i.e. not via adult BMI) based on multivariable MR (MVMR) estimates (CAD OR:1.02, 95% CI:0.86-1.22, T2D OR:1.16, 95% CI:0.74-1.82). In the MVMR analysis of breast cancer risk, there was strong evidence of a protective direct effect for early BMI (OR:0.59, 95% CI:0.50-0.71), although adult BMI did not appear to have a direct effect on this outcome (OR:1.08, 95% CI:0.93-1.27). Adding age of menarche as an additional exposure provided weak evidence of a total causal effect (UVMR OR:0.98, 95% CI:0.91-1.06) but strong evidence of a direct causal effect, independent of early and adult BMI (MVMR OR:0.90, 95% CI:0.85-0.95). Weak evidence of a causal effect was observed in the MVMR analysis of prostate cancer (early life BMI OR:1.06, 95% CI:0.81-1.40, adult BMI OR:0.87, 95% CI:0.70-1.08). Conclusions: Our findings suggest that increased CAD and T2D risk attributed to early life adiposity can be mitigated if individuals reduce their weight in later life. However, having a low BMI during childhood may increase risk of breast cancer regardless of changes to weight in later life, with timing of puberty also putatively playing an important role. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Integrative Epidemiology Unit which receives funding from the UK Medical Research Council and the University of Bristol (MC_UU_00011/1, MC_UU_00011/2 and MC_UU_00011/3). T.G.R is a UKRI Innovation Research Fellow (MR/S003886/1). ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Yes All data analysed in our study was made available from the UK Biobank study. Summary statistics will be made publicly available via the MR-Base platform. | |
| Cold Spring Harbor Laboratory Press | |
| 2019 | |
| Preimpreso | |
| https://www.medrxiv.org/content/10.1101/19008011v1 | |
| Inglés | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Artículos científicos |
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