TY - JOUR
T1 - Mendelian randomization study implicates inflammaging biomarkers in retinal vasculature, cardiovascular diseases, and longevity
AU - Villaplana-Velasco, Ana
AU - Perrot, Nicolas
AU - Hang, Yu
AU - Chong, Michael
AU - Trucco, Emanuele
AU - Mookiah, Muthu R.K.
AU - Nelson, Walter
AU - Petch, Jeremy
AU - Gerstein, Hertzel C.
AU - Raina, Parminder
AU - Yusuf, Salim
AU - Bernabeu, Miguel O.
AU - Tenesa, Albert
AU - Rawlik, Konrad
AU - Pare, Guillaume
AU - Doney, Alexander
AU - Pairo-Castineira, Erola
AU - Pigeyre, Marie
N1 - Publisher Copyright:
© (2025), (American Association for the Advancement of Science). All rights reserved.
PY - 2025/10/24
Y1 - 2025/10/24
N2 - With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (Df) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of Df on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1. We found negative genetic correlations between Df and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of Df using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG–Fc receptor IIb, which link higher inflammation to lower Df, increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to prevention and treatment.
AB - With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension (Df) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of Df on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1. We found negative genetic correlations between Df and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of Df using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG–Fc receptor IIb, which link higher inflammation to lower Df, increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to prevention and treatment.
UR - https://www.scopus.com/pages/publications/105019999911
U2 - 10.1126/sciadv.adu1985
DO - 10.1126/sciadv.adu1985
M3 - Article
C2 - 41134885
AN - SCOPUS:105019999911
SN - 2375-2548
VL - 11
SP - 1
EP - 15
JO - Science Advances
JF - Science Advances
IS - 43
M1 - eadu1985
ER -
