Genome-wide analysis of brain age identifies 59 associated loci and unveils relationships with mental and physical health.
Authors
Affiliations (8)
Affiliations (8)
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany. [email protected].
- LIFE-Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany. [email protected].
- Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
- LIFE-Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany.
- Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Leipzig, Germany.
- Cognitive Neurology, University of Leipzig Medical Center & Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
- Stanley Center for Psychiatric Research, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
- Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin, Berlin, Germany.
Abstract
Neuroimaging and machine learning are advancing research into the mechanisms of biological aging. In this field, 'brain age gap' has emerged as a promising magnetic resonance imaging-based biomarker that quantifies the deviation between an individual's biological and chronological age of the brain. Here we conducted an in-depth genomic analysis of the brain age gap and its relationships with over 1,000 health traits. Genome-wide analyses in up to 56,348 individuals unveiled a heritability of 23-29% attributable to common genetic variants and highlighted 59 associated loci (39 novel). The leading locus encompasses MAPT, encoding the tau protein central to Alzheimer's disease. Genetic correlations revealed relationships with mental health, physical health, lifestyle and socioeconomic traits, including depressed mood, diabetes, alcohol intake and income. Mendelian randomization indicated a causal role of high blood pressure and type 2 diabetes in accelerated brain aging. Our study highlights key genes and pathways related to neurogenesis, immune-system-related processes and small GTPase binding, laying the foundation for further mechanistic exploration.