The Genetic Architecture of Multimodal Human Brain Age

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Mar 24

PMID 38521789

Authors

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

Affiliations

Soon will be listed here.

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). 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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