The genetic architecture of multimodal human brain age
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 < 5x10(-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.
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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, M. D., Shou, H., Thompson, P. M., Shen, L., Toga, A. W., & Davatzikos, C. (2024). The genetic architecture of multimodal human brain age. Nature Communications, 15(1), Article 2604. https://doi.org/10.1038/s41467-024-46796-6
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WOS:001190084300021
2024-03-23
15
1
2604
REVIEWED
EPFL
| Funder | Grant Number |
U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) | RF1 AG054409 |
Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California - NIA | |