Genetics of brain age suggest an overlap with common brain disorders
Dennis van der Meer,
Nhat Trung Doan,
Martina J. Lund,
Deanna M. Barch,
Mona K. Beyer,
Christine L. Brandt,
Elisabeth G. Celius,
Anders M. Dale,
Dominique J.-F. de Quervain,
Pasquale Di Carlo,
Erlend S. Dørum,
Asta K Håberg,
Hanne F. Harbo,
Catharina A. Hartman,
Pieter J. Hoekstra,
Einar A. Høgestøl,
Erik G. Jönsson,
Karolinska Schizophrenia Project (KaSP),
Nils Inge Landrø,
Stephanie Le Hellard,
Luigi A. Maglanoc,
Ulrik F. Malt,
Linn B. Norbom,
Jan Egil Nordvik,
Alexey A. Shadrin,
Olav B. Smeland,
Vidar M. Steen,
Kristine M. Ulrichsen,
Georg C. Ziegler,
Ole A. Andreassen,
Lars T. Westlye,
for the Alzheimer’s Disease Neuroimaging Initiative,
for the Pediatric Imaging, Neurocognition and Genetics Study,
for the AddNeuroMed consortium
Posted 17 Apr 2018
bioRxiv DOI: 10.1101/303164 (published DOI: 10.1038/s41593-019-0471-7)
Posted 17 Apr 2018
Numerous genetic and environmental factors contribute to psychiatric disorders and other brain disorders. Common risk factors likely converge on biological pathways regulating the optimization of brain structure and function across the lifespan. Here, using structural magnetic resonance imaging and machine learning, we estimated the gap between brain age and chronological age in 36,891 individuals aged 3 to 96 years, including individuals with different brain disorders. We show that several disorders are associated with accentuated brain aging, with strongest effects in schizophrenia, multiple sclerosis and dementia, and document differential regional patterns of brain age gaps between disorders. In 16,269 healthy adult individuals, we show that brain age gap is heritable with a polygenic architecture overlapping those observed in common brain disorders. Our results identify brain age gap as a genetically modulated trait that offers a window into shared and distinct mechanisms in different brain disorders.
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