The genetic architecture of multimodal human brain age

Junhao Wen; Bingxin Zhao; Zhijian Yang; Guray Erus; Ioanna Skampardoni; Elizabeth Mamourian; Yuhan Cui; Gyujoon Hwang; Jingxuan Bao; Aleix Boquet-Pujadas; Zhen Zhou; Yogasudha Veturi; Marylyn D. Ritchie; Haochang Shou; Paul M. Thompson; Li Shen; Arthur W. Toga; Christos Davatzikos

doi:10.1038/s41467-024-46796-6

The genetic architecture of multimodal human brain age

Junhao Wen
, Bingxin Zhao
, Zhijian Yang
, Guray Erus
, Ioanna Skampardoni
, Elizabeth Mamourian
, Yuhan Cui
, Gyujoon Hwang
, Jingxuan Bao
, Aleix Boquet-Pujadas
, Zhen Zhou
, Yogasudha Veturi
, Marylyn D. Ritchie
, Haochang Shou
, Paul M. Thompson
, Li Shen
, Arthur W. Toga
, Christos Davatzikos

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

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.

Original language	English (US)
Article number	2604
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-46796-6
State	Published - Dec 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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Cite this

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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abstract = "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 = "Junhao Wen and Bingxin Zhao and Zhijian Yang and Guray Erus and Ioanna Skampardoni and Elizabeth Mamourian and Yuhan Cui and Gyujoon Hwang and Jingxuan Bao and Aleix Boquet-Pujadas and Zhen Zhou and Yogasudha Veturi and Ritchie, \{Marylyn D.\} and Haochang Shou and Thompson, \{Paul M.\} and Li Shen and Toga, \{Arthur W.\} and Christos Davatzikos",

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The genetic architecture of multimodal human brain age

Abstract

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