Cargando…
The Genetic Architecture of Multimodal Human Brain Age
The complex biological mechanisms underlying human brain aging remain incompletely understood, involving multiple body organs and chronic diseases. In this study, we used multimodal magnetic resonance imaging and artificial intelligence to examine the genetic architecture of the brain age gap (BAG)...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274645/ https://www.ncbi.nlm.nih.gov/pubmed/37333190 http://dx.doi.org/10.1101/2023.04.13.536818 |
_version_ | 1785059772756656128 |
---|---|
author | Wen, Junhao Zhao, Bingxin Yang, Zhijian Erus, Guray Skampardoni, Ioanna Mamourian, Elizabeth Cui, Yuhan Hwang, Gyujoon Bao, Jingxuan Boquet-Pujadas, Aleix Zhou, Zhen Veturi, Yogasudha Ritchie, Marylyn D. Shou, Haochang Thompson, Paul M. Shen, Li Toga, Arthur W. Davatzikos, Christos |
author_facet | Wen, Junhao Zhao, Bingxin Yang, Zhijian Erus, Guray Skampardoni, Ioanna Mamourian, Elizabeth Cui, Yuhan Hwang, Gyujoon Bao, Jingxuan Boquet-Pujadas, Aleix Zhou, Zhen Veturi, Yogasudha Ritchie, Marylyn D. Shou, Haochang Thompson, Paul M. Shen, Li Toga, Arthur W. Davatzikos, Christos |
author_sort | Wen, Junhao |
collection | PubMed |
description | The complex biological mechanisms underlying human brain aging remain incompletely understood, involving multiple body organs and chronic diseases. In this study, we used multimodal magnetic resonance imaging and artificial intelligence to examine the genetic architecture of the brain age gap (BAG) derived from gray matter volume (GM-BAG, N=31,557 European ancestry), white matter microstructure (WM-BAG, N=31,674), and functional connectivity (FC-BAG, N=32,017). 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 showed the highest heritability enrichment for genetic variants in conserved regions, whereas WM-BAG exhibited the highest heritability enrichment in the 5’ untranslated regions; oligodendrocytes and astrocytes, but not neurons, showed significant heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several exposure variables on brain aging, such as type 2 diabetes on GM-BAG (odds ratio=1.05 [1.01, 1.09], P-value=1.96×10(−2)) and AD on WM-BAG (odds ratio=1.04 [1.02, 1.05], P-value=7.18×10(−5)). Overall, our results provide valuable insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at the MEDICINE knowledge portal: https://labs.loni.usc.edu/medicine. |
format | Online Article Text |
id | pubmed-10274645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-102746452023-06-17 The Genetic Architecture of Multimodal Human Brain Age Wen, Junhao Zhao, Bingxin Yang, Zhijian Erus, Guray Skampardoni, Ioanna Mamourian, Elizabeth Cui, Yuhan Hwang, Gyujoon Bao, Jingxuan Boquet-Pujadas, Aleix Zhou, Zhen Veturi, Yogasudha Ritchie, Marylyn D. Shou, Haochang Thompson, Paul M. Shen, Li Toga, Arthur W. Davatzikos, Christos bioRxiv Article The complex biological mechanisms underlying human brain aging remain incompletely understood, involving multiple body organs and chronic diseases. In this study, we used multimodal magnetic resonance imaging and artificial intelligence to examine the genetic architecture of the brain age gap (BAG) derived from gray matter volume (GM-BAG, N=31,557 European ancestry), white matter microstructure (WM-BAG, N=31,674), and functional connectivity (FC-BAG, N=32,017). 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 showed the highest heritability enrichment for genetic variants in conserved regions, whereas WM-BAG exhibited the highest heritability enrichment in the 5’ untranslated regions; oligodendrocytes and astrocytes, but not neurons, showed significant heritability enrichment in WM and FC-BAG, respectively. Mendelian randomization identified potential causal effects of several exposure variables on brain aging, such as type 2 diabetes on GM-BAG (odds ratio=1.05 [1.01, 1.09], P-value=1.96×10(−2)) and AD on WM-BAG (odds ratio=1.04 [1.02, 1.05], P-value=7.18×10(−5)). Overall, our results provide valuable insights into the genetics of human brain aging, with clinical implications for potential lifestyle and therapeutic interventions. All results are publicly available at the MEDICINE knowledge portal: https://labs.loni.usc.edu/medicine. Cold Spring Harbor Laboratory 2023-09-30 /pmc/articles/PMC10274645/ /pubmed/37333190 http://dx.doi.org/10.1101/2023.04.13.536818 Text en https://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Wen, Junhao Zhao, Bingxin Yang, Zhijian Erus, Guray Skampardoni, Ioanna Mamourian, Elizabeth Cui, Yuhan Hwang, Gyujoon Bao, Jingxuan Boquet-Pujadas, Aleix Zhou, Zhen Veturi, Yogasudha Ritchie, Marylyn D. Shou, Haochang Thompson, Paul M. Shen, Li Toga, Arthur W. Davatzikos, Christos The Genetic Architecture of Multimodal Human Brain Age |
title | The Genetic Architecture of Multimodal Human Brain Age |
title_full | The Genetic Architecture of Multimodal Human Brain Age |
title_fullStr | The Genetic Architecture of Multimodal Human Brain Age |
title_full_unstemmed | The Genetic Architecture of Multimodal Human Brain Age |
title_short | The Genetic Architecture of Multimodal Human Brain Age |
title_sort | genetic architecture of multimodal human brain age |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10274645/ https://www.ncbi.nlm.nih.gov/pubmed/37333190 http://dx.doi.org/10.1101/2023.04.13.536818 |
work_keys_str_mv | AT wenjunhao thegeneticarchitectureofmultimodalhumanbrainage AT zhaobingxin thegeneticarchitectureofmultimodalhumanbrainage AT yangzhijian thegeneticarchitectureofmultimodalhumanbrainage AT erusguray thegeneticarchitectureofmultimodalhumanbrainage AT skampardoniioanna thegeneticarchitectureofmultimodalhumanbrainage AT mamourianelizabeth thegeneticarchitectureofmultimodalhumanbrainage AT cuiyuhan thegeneticarchitectureofmultimodalhumanbrainage AT hwanggyujoon thegeneticarchitectureofmultimodalhumanbrainage AT baojingxuan thegeneticarchitectureofmultimodalhumanbrainage AT boquetpujadasaleix thegeneticarchitectureofmultimodalhumanbrainage AT zhouzhen thegeneticarchitectureofmultimodalhumanbrainage AT veturiyogasudha thegeneticarchitectureofmultimodalhumanbrainage AT ritchiemarylynd thegeneticarchitectureofmultimodalhumanbrainage AT shouhaochang thegeneticarchitectureofmultimodalhumanbrainage AT thompsonpaulm thegeneticarchitectureofmultimodalhumanbrainage AT shenli thegeneticarchitectureofmultimodalhumanbrainage AT togaarthurw thegeneticarchitectureofmultimodalhumanbrainage AT davatzikoschristos thegeneticarchitectureofmultimodalhumanbrainage AT wenjunhao geneticarchitectureofmultimodalhumanbrainage AT zhaobingxin geneticarchitectureofmultimodalhumanbrainage AT yangzhijian geneticarchitectureofmultimodalhumanbrainage AT erusguray geneticarchitectureofmultimodalhumanbrainage AT skampardoniioanna geneticarchitectureofmultimodalhumanbrainage AT mamourianelizabeth geneticarchitectureofmultimodalhumanbrainage AT cuiyuhan geneticarchitectureofmultimodalhumanbrainage AT hwanggyujoon geneticarchitectureofmultimodalhumanbrainage AT baojingxuan geneticarchitectureofmultimodalhumanbrainage AT boquetpujadasaleix geneticarchitectureofmultimodalhumanbrainage AT zhouzhen geneticarchitectureofmultimodalhumanbrainage AT veturiyogasudha geneticarchitectureofmultimodalhumanbrainage AT ritchiemarylynd geneticarchitectureofmultimodalhumanbrainage AT shouhaochang geneticarchitectureofmultimodalhumanbrainage AT thompsonpaulm geneticarchitectureofmultimodalhumanbrainage AT shenli geneticarchitectureofmultimodalhumanbrainage AT togaarthurw geneticarchitectureofmultimodalhumanbrainage AT davatzikoschristos geneticarchitectureofmultimodalhumanbrainage |