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Genetics of brain age suggest an overlap with common brain disorders

By Tobias Kaufmann, Dennis van der Meer, Nhat Trung Doan, Emanuel Schwarz, Martina J. Lund, Ingrid Agartz, Dag Alnaes, Deanna M. Barch, Ramona Baur-Streubel, Alessandro Bertolino, Francesco Bettella, Mona K. Beyer, Erlend Bøen, Stefan Borgwardt, Christine L. Brandt, Jan Buitelaar, Elisabeth Gulowsen Celius, Simon Cervenka, Annette Conzelmann, Aldo Córdova-Palomera, Anders M. Dale, Dominique J.-F. de Quervain, Pasquale Di Carlo, Srdjan Djurovic, Erlend S. Dørum, Sarah Eisenacher, Torbjørn Elvsåshagen, Thomas Espeseth, Helena Fatouros-Bergman, Lena Flyckt, Barbara Franke, Oleksandr Frei, Beathe Haatveit, Asta K. Håberg, Hanne Flinstad Harbo, Catharina A. Hartman, Dirk Heslenfeld, Pieter J Hoekstra, Einar A. Høgestøl, Terry Jernigan, Rune Jonassen, Erik G. Jönsson, Karolinska Schizophrenia Project (KaSP), Peter Kirsch, Iwona Kłoszewska, Knut-Kristian Kolskår, Nils Inge Landrø, Stephanie Le Hellard, Klaus-Peter Lesch, Simon Lovestone, Arvid Lundervold, Astri J. Lundervold, Luigi A. Maglanoc, Ulrik F. Malt, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Torgeir Moberget, Linn B. Norbom, Jan Egil Nordvik, Lars Nyberg, Jaap Oosterlaan, Marco Papalino, Andreas Papassotiropoulos, Paul Pauli, Giulio Pergola, Karin Persson, Genevieve Richard, Jaroslav Rokicki, Anne-Marthe Sanders, Geir Selbæk, Alexey A. Shadrin, Olav B Smeland, Hilkka Soininen, Piotr Sowa, Vidar M. Steen, Magda Tsolaki, Kristine M. Ulrichsen, Bruno Vellas, Lei Wang, Eric Westman, Georg C. Ziegler, Mathias Zink, 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)

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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