Human genetic risk for major depressive disorder implicates motor cortex PVALB⁺ inhibitory neurons
· 2026-09-10 · 原文
DOI：10.64898/2026.09.08.26362568v1?rss=1
Major depressive disorder (MDD) is highly polygenic, but the cellular and anatomical contexts through which inherited risk contributes to disease biology remain incompletely understood. Here we integrated large-scale MDD genome-wide association studies with an adult human brain single-cell discovery atlas and five independent replication atlases spanning brain regions, developmental stages, species, and disease states, comprising more than five million cells and nuclei. Across complementary polygenic mapping frameworks, MDD genetic signals were preferentially enriched in neuronal populations and consistently prioritized the primary motor cortex (M1) as a key anatomical context of risk. Subtype-level analyses highlighted PVALB+ inhibitory neurons and Ex-L2/4 excitatory neurons, with integra
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1. 人话版
Major depressive disorder (MDD) is highly polygenic, but the cellular and anatomical contexts through which inherited risk contributes to disease biology remain incompletely understood.
Here we integrated large-scale MDD genome-wide association studies with an adult human brain single-cell discovery atlas and five independent replication atlases spanning brain regions, developmental stages, species, and disease states, comprising more than five million cells and nuclei.
2. 领域脉络
来源板块：板块一 · 研究前沿。
3. 机制拆解
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4. 证据与数字
Across complementary polygenic mapping frameworks, MDD genetic signals were preferentially enriched in neuronal populations and consistently prioritized the primary motor cortex (M1) as a key anatomical context of risk.
Subtype-level analyses highlighted PVALB+ inhibitory neurons and Ex-L2/4 excitatory neurons, with integra
5. 反例与边界
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6. 跨领域连接与意外收获
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7. 可复用方法
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8. 术语表
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