| 1. |
- Sumpter, N. A., et al.
(author)
-
Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout
- 2023
-
In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:5, s. 816-825
-
Journal article (peer-reviewed)abstract
- Objective. To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods. A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results. The PRS was associated with earlier age at gout onset in men (beta = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; beta = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; beta = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (beta = 0.07 [95% CI -2.32, 2.45] in European women; beta = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; beta -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (beta = -2.42 [95% CI -3.37, -1.46] and beta = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (beta = -1.79 [95% CI -4.74, 1.16]). Conclusion. Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.
|
|
| 2. |
- Green, C., et al.
(author)
-
A Horizon Scan to Support Chemical Pollution-Related Policymaking for Sustainable and Climate-Resilient Economies
- 2023
-
In: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 42:6, s. 1212-1228
-
Journal article (peer-reviewed)abstract
- While chemicals are vital to modern society through materials, agriculture, textiles, new technology, medicines, and consumer goods, their use is not without risks. Unfortunately, our resources seem inadequate to address the breadth of chemical challenges to the environment and human health. Therefore, it is important we use our intelligence and knowledge wisely to prepare for what lies ahead. The present study used a Delphi-style approach to horizon-scan future chemical threats that need to be considered in the setting of chemicals and environmental policy, which involved a multidisciplinary, multisectoral, and multinational panel of 25 scientists and practitioners (mainly from the United Kingdom, Europe, and other industrialized nations) in a three-stage process. Fifteen issues were shortlisted (from a nominated list of 48), considered by the panel to hold global relevance. The issues span from the need for new chemical manufacturing (including transitioning to non-fossil-fuel feedstocks); challenges from novel materials, food imports, landfills, and tire wear; and opportunities from artificial intelligence, greater data transparency, and the weight-of-evidence approach. The 15 issues can be divided into three classes: new perspectives on historic but insufficiently appreciated chemicals/issues, new or relatively new products and their associated industries, and thinking through approaches we can use to meet these challenges. Chemicals are one threat among many that influence the environment and human health, and interlinkages with wider issues such as climate change and how we mitigate these were clear in this exercise. The horizon scan highlights the value of thinking broadly and consulting widely, considering systems approaches to ensure that interventions appreciate synergies and avoid harmful trade-offs in other areas. We recommend further collaboration between researchers, industry, regulators, and policymakers to perform horizon scanning to inform policymaking, to develop our ability to meet these challenges, and especially to extend the approach to consider also concerns from countries with developing economies. Environ Toxicol Chem 2023;00:1-17. (c) 2023 Crown copyright and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland.
|
|
