Body mass index and heart failure risk: a cohort study in 1.5 million individuals and Mendelian randomisation analysis
Published: 25 September 2020, BMJ (pre-print)
Authors: Thomas Lumbers, Michail Katsoulis, Albert Henry, Ify Mordi, Chim Lang, Harry Hemingway, Claudia Langenberg, Michael Holmes, Naveed Sattar
Elevated body mass index (BMI) is a known risk factor for heart failure (HF), however, the underlying mechanisms are incompletely understood. The aim of this study was to investigate the role of common HF risk factors as potential mediators. Methods and Results Electronic health record data from primary care, hospital admissions and death registrations in England were used to perform an observational analysis. Data for 1.5 million individuals aged 18 years or older, with BMI measurements and free from heart failure at baseline, were included between 1998 and 2016. Cox models were used to estimate the association between BMI and HF with and without adjustment for atrial fibrillation (AF), diabetes mellitus (DM), coronary heart disease (CHD), and hypertension (HTN). Univariable and multivariable two-sample Mendelian randomisation was performed to estimate causal effects. Among non-underweight individuals, BMI was positively associated with HF with a 1-SD (~ 4.8kg/m2) higher BMI associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI] 1.30, 1.32). Genetically predicted BMI yielded a causal odds ratio (OR) of 1.64 per 4.8 kg/m2 BMI (95% CI 1.58, 1.70) which attenuated by 41% (to OR of 1.38 (95% CI 1.31 - 1.45), when simultaneously accounting for AF, DM, CHD and SBP. Conclusion About 40% of the excess risk of HF due to adiposity is driven by SBP, AF, DM and CHD. These findings highlight the importance of the prevention and treatment of excess adiposity and downstream HF risk factors to prevent HF, even in people in whom the above risk factors are well managed.
Read the pre-print here: https://doi.org/10.1101/2020.09.23.20200360
Sleep duration and risk of overall and 22 site‐specific cancers: A Mendelian randomization study
Published: 7 September 2020, Cancer Epidemiology
Authors: Olga E. Titova, Karl Michaëlsson, Mathew Vithayathil, Amy M. Mason, Siddhartha Kar, Stephen Burgess, Susanna C. Larsson
Studies of sleep duration in relation to the risk of site‐specific cancers other than breast cancer are scarce. Furthermore, the available results are inconclusive and the causality remains unclear. We aimed to investigate the potential causal associations of sleep duration with overall and site‐specific cancers using the Mendelian randomization (MR) design. Single‐nucleotide polymorphisms associated with the sleep traits identified from a genome‐wide association study were used as instrumental variables to estimate the association with overall cancer and 22 site‐specific cancers among 367 586 UK Biobank participants. A replication analysis was performed using data from the FinnGen consortium (up to 121 579 individuals). There was suggestive evidence that genetic liability to short‐sleep duration was associated with higher odds of cancers of the stomach (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.15‐4.30; P = .018), pancreas (OR, 2.18; 95% CI, 1.32‐3.62; P = .002) and colorectum (OR, 1.48; 95% CI, 1.12‐1.95; P = .006), but with lower odds of multiple myeloma (OR, 0.47; 95% CI, 0.22‐0.99; P = .047). Suggestive evidence of association of genetic liability to long‐sleep duration with lower odds of pancreatic cancer (OR, 0.44; 95% CI, 0.25‐0.79; P = .005) and kidney cancer (OR, 0.44; 95% CI, 0.21‐0.90; P = .025) was observed. However, none of these associations passed the multiple comparison threshold and two‐sample MR analysis using FinnGen data did not confirm these findings. In conclusion, this MR study does not provide strong evidence to support causal associations of sleep duration with risk of overall and site‐specific cancers. Further MR studies are required.
Read the full paper here: https://doi.org/10.1002/ijc.33286
UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER
We are delighted to announce that the paper ‘UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER’, written by Spiros Denaxas et colleagues and published on the Journal of the American Medical Informatics Association in December 2019, has been selected for the International Medical Informatics Association (IMIA) Yearbook of Medical Informatics for 2020.