Mohsen Ghanbari

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.

Sep 8, 2024 | nature.com | Shahzad Ahmad |Aniket Mishra |Marisol Herrera-Rivero |Joshua C. Bis |Myriam Fornage |Gennady V Roshchupkin | +13 more

AbstractNeurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders.

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.

Oct 16, 2023 | onlinelibrary.wiley.com | Isabel K. Schuurmans |Mohsen Ghanbari |M. Arfan Ikram |Annemarie I. Luik

Supporting Information Filename Description pcn13608-sup-0001-Supinfo.docxWord 2007 document , 102.2 KB Figure S1. Flowchart Table S1. Pearson correlation between plasma markers Table S2. Cross-sectional association between biomarkers of neurodegenerative disease and depressive symptom, standardized estimates Table S3. Longitudinal association between biomarkers of neurodegenerative disease and incidence of depression, standardized estimates

Jul 18, 2023 | mdpi.com | Kan Wang |Mohsen Ghanbari |Fariba Ahmadizar |Mina Shahisavandi

This is an early access version, the complete PDF, HTML, and XML versions will be available soon. Open AccessReviewby 1,†, 1,†, 1 and 2,* 1Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands2Department of Data Science & Biostatistics, Julius Global Health, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands*Author to whom correspondence should be addressed. †These authors contributed equally to this work.