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与一生中大脑结构纵向变化相关的遗传变异。

Genetic variants associated with longitudinal changes in brain structure across the lifespan.

机构信息

Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.

Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU Amsterdam, Amsterdam, The Netherlands.

出版信息

Nat Neurosci. 2022 Apr;25(4):421-432. doi: 10.1038/s41593-022-01042-4. Epub 2022 Apr 5.

DOI:10.1038/s41593-022-01042-4
PMID:35383335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10040206/
Abstract

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.

摘要

人类大脑结构在整个生命周期中发生变化。大脑生长的改变或衰退速度的改变与广泛的精神疾病、发育和神经退行性疾病有关。在这项研究中，我们确定了常见的遗传变异，这些变异影响大脑形态在整个生命周期中的生长或萎缩速度。我们利用来自 15640 个人的纵向磁共振成像数据来计算 15 个大脑结构的变化率。最显著的鉴定基因 GPR139、DACH1 和 APOE 与代谢过程有关。我们证明了与抑郁、精神分裂症、认知功能、失眠、身高、体重指数和吸烟的全球遗传重叠。基因集研究结果表明，大脑变化的速度既与早期大脑发育有关，也与神经退行性过程有关。确定参与结构脑变化的变异可能有助于确定最佳和功能失调的大脑发育和衰老的潜在生物学途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21e1/10040206/2beef619d134/nihms-1784902-f0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21e1/10040206/9b2ffcffd11c/nihms-1784902-f0007.jpg
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2
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3
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medRxiv. 2025 Aug 12:2025.08.10.25333373. doi: 10.1101/2025.08.10.25333373.
4
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Mol Psychiatry. 2025 Aug 19. doi: 10.1038/s41380-025-03136-4.
5
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6
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