The genetic architecture of multimodal human brain age. Nat Commun 2024 Mar 23;15(1):2604
Date
03/24/2024Pubmed ID
38521789Pubmed Central ID
PMC10960798DOI
10.1038/s41467-024-46796-6Scopus ID
2-s2.0-85188443845 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
The complex biological mechanisms underlying human brain aging remain incompletely understood. This study investigated the genetic architecture of three brain age gaps (BAG) derived from gray matter volume (GM-BAG), white matter microstructure (WM-BAG), and functional connectivity (FC-BAG). We identified sixteen genomic loci that reached genome-wide significance (P-value < 5×10-8). A gene-drug-disease network highlighted genes linked to GM-BAG for treating neurodegenerative and neuropsychiatric disorders and WM-BAG genes for cancer therapy. GM-BAG displayed the most pronounced heritability enrichment in genetic variants within conserved regions. Oligodendrocytes and astrocytes, but not neurons, exhibited notable heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several chronic diseases on brain aging, such as type 2 diabetes on GM-BAG and AD on WM-BAG. Our results provide insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at https://labs.loni.usc.edu/medicine .
Author List
Wen J, Zhao B, Yang Z, Erus G, Skampardoni I, Mamourian E, Cui Y, Hwang G, Bao J, Boquet-Pujadas A, Zhou Z, Veturi Y, Ritchie MD, Shou H, Thompson PM, Shen L, Toga AW, Davatzikos CAuthor
Gyujoon Hwang PhD Assistant Professor in the Psychiatry and Behavioral Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
BrainDiabetes Mellitus, Type 2
Gray Matter
Humans
Magnetic Resonance Imaging
Mendelian Randomization Analysis
White Matter
