Cornelia van Duijn

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.

Jul 10, 2024 | medrxiv.org | Xin You Tai |Sofia Toniolo |David Llewellyn |Cornelia van Duijn

The authors have declared no competing interest. This work was funded by the Wellcome Trust (Wellcome Trust PhD clinical fellowship to XYT and Wellcome Trust Principal Research Fellowship to MH [206330/Z/17/Z]) and MRC (Clinician Scientist Fellowship to S.M. [MR/P00878/X]) and by the Oxford NIHR Biomedical Research Centre. I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Mar 6, 2024 | nature.com | Minna K. Karjalainen |Eeva Sliz |Elias Allara |Weihua Zhang |Pekka Jousilahti |Kati Kristiansson | +46 more

AbstractGenome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1,2,3,4,5,6,7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8,9,10,11.

Feb 27, 2024 | medrxiv.org | Lazaros Belbasis |Sam Morris |Derrick Bennett |Cornelia van Duijn

The authors have declared no competing interest. Lazaros Belbasis is supported by an NDPH Early Career Research Fellowship. I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.