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The genetic architecture of multimodal human brain age

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

in 45 / 45/43 / 631/114/1305 / 692/308/2056 / 692/53/2423 / Aging / Astrocytes / Brain / Brain architecture / Cancer therapies / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 / Genes / Genetic diversity / Genetic variance / Genetics / Gray Matter / Heritability / Humanities and Social Sciences / Humans / Magnetic Resonance Imaging - methods / Mendelian Randomization Analysis / Mental disorders / multidisciplinary / Neural networks / Oligodendrocytes / Science / Science (multidisciplinary) / Substantia alba / Substantia grisea / Therapeutic applications / White Matter - physiology

2024

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2024

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2024

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Journal Article

The genetic architecture of multimodal human brain age

Hwang, Gyujoon,

Zhou, Zhen,

Boquet-Pujadas, Aleix,

Wen, Junhao,

Zhao, Bingxin,

Skampardoni, Ioanna,

Veturi, Yogasudha,

Mamourian, Elizabeth,

Cui, Yuhan,

Bao, Jingxuan,

Shen, Li,

Yang, Zhijian,

Erus, Guray,

Ritchie, Marylyn D.,

Toga, Arthur W.,

Davatzikos, Christos,

Shou, Haochang,

Thompson, Paul M.

2024

Overview

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 . The biological basis of brain aging is not well understood, but it has implications for human health. Here, the authors explore the genetic basis of human brain aging, finding genetic variants, genes and potential causal relationships with disease.

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Publisher

Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

Subject

/ 45/43

/ Aging

/ Brain