David Hunter
Host at Joint Action
Co-Editor-in-Chief at Osteoarthritis and Cartilage
Osteoarthritis scientist and clinician. aka Joint Doctor. co-Editor in Chief @OACJournal. Host of @jointactionorg podcast
Articles
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2 months ago |
nature.com | M. Austin Argentieri |Najaf Amin |Alejo J Nevado-Holgado |William Sproviero |Jennifer Collister |Sarai Keestra | +7 more
Both environmental exposures and genetics are known to play important roles in shaping human aging. Here we aimed to quantify the relative contributions of environment (referred to as the exposome) and genetics to aging and premature mortality. To systematically identify environmental exposures associated with aging in the UK Biobank, we first conducted an exposome-wide analysis of all-cause mortality (n = 492,567) and then assessed the associations of these exposures with a proteomic age clock (n = 45,441), identifying 25 independent exposures associated with mortality and proteomic aging. These exposures were also associated with incident age-related multimorbidity, aging biomarkers and major disease risk factors. Compared with information on age and sex, polygenic risk scores for 22 major diseases explained less than 2 percentage points of additional mortality variation, whereas the exposome explained an additional 17 percentage points. Polygenic risk explained a greater proportion of variation (10.3–26.2%) compared with the exposome for incidence of dementias and breast, prostate and colorectal cancers, whereas the exposome explained a greater proportion of variation (5.5–49.4%) compared with polygenic risk for incidence of diseases of the lung, heart and liver. Our findings provide a comprehensive map of the contributions of environment and genetics to mortality and incidence of common age-related diseases, suggesting that the exposome shapes distinct patterns of disease and mortality risk, irrespective of polygenic disease risk. Based on a systematic analysis of environmental exposures associated with aging and mortality in the UK Biobank, the relative contributions of such exposures and genetic risk for mortality and a range of age-related diseases were compared, highlighting the potential beneficial effects of environment-focused interventions.
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Nov 9, 2023 |
nature.com | Thomas Sellers Jr. |David Hunter |Ian Thompson |Robert Hamilton |Ana Francisca Vega |Eric A. Klein | +98 more
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups. A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.
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We need some real policy reform, especially around complex chronic diseases like #osteoarthritis. The band-aid solutions being provided by both of the major parties are not going to help. https://t.co/ko8V1M09Ex via @ConversationEDU
Are joint injections worth it for knee #osteoarthritis? 🤔 Dr. Bruno da Costa reveals the shocking gaps in evidence, placebo effects & commercial bias behind common treatments. An eye-opening new episode of @jointactionorg 🔗 Tune in: https://t.co/Z0aKe67Gld https://t.co/bto4iQ4BiI
RT @giovanni_ef: Massive effort from an incredible team to deliver a comprehensive summary of all available cost-effectiveness data for ost…
