美国约翰霍普金斯大学Daniel R. Weinberger、Shizhong Han、Kynon J. M. Benjamin研究组，通过对神经畸形美国死亡黑人大脑基因表达进行分析揭示了基因谱系的影响。相关论文于2024年5月20日发表在《自然-神经科学》杂志上。

研究人员研究了基因来源对混血美国黑人神经畸形个体死后，脑组织中基因表达和DNA甲基化的影响，以确定祖先依赖性和非依赖性的影响。与祖先相关的差异表达基因（DEGs）、转录本和基因网络虽然与神经元无关，但富含与免疫反应和血管组织相关的基因则与高达26%的缺血性中风遗传率、27%的帕金森病遗传率和30%的阿尔茨海默病遗传率有关。

与祖先相关的DEGs在各种免疫相关遗传形状中也明显存在富集，但在精神相关性状方面则具有耗竭性。研究还比较了美国黑人和非西班牙裔白人，验证了大多数与祖先相关的DEGs。该研究结果阐明了遗传祖先对人类大脑中基因表达差异的影响程度，以及对脑部疾病发病的影响。

研究人员表示，基因组变异的祖先差异会影响基因表达调控；然而，大多数基因表达研究仅限于欧洲样本人群，或为确定与祖先无关的关联而进行调整。

附：英文原文

Title: Analysis of gene expression in the postmortem brain of neurotypical Black Americans reveals contributions of genetic ancestry

Author: Benjamin, Kynon J. M., Chen, Qiang, Eagles, Nicholas J., Huuki-Myers, Louise A., Collado-Torres, Leonardo, Stolz, Joshua M., Pertea, Geo, Shin, Joo Heon, Paquola, Apu C. M., Hyde, Thomas M., Kleinman, Joel E., Jaffe, Andrew E., Han, Shizhong, Weinberger, Daniel R.

Issue&Volume: 2024-05-20

Abstract: Ancestral differences in genomic variation affect the regulation of gene expression; however, most gene expression studies have been limited to European ancestry samples or adjusted to identify ancestry-independent associations. Here, we instead examined the impact of genetic ancestry on gene expression and DNA methylation in the postmortem brain tissue of admixed Black American neurotypical individuals to identify ancestry-dependent and ancestry-independent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts and gene networks, while notably not implicating neurons, are enriched for genes related to the immune response and vascular tissue and explain up to 26% of heritability for ischemic stroke, 27% of heritability for Parkinson disease and 30% of heritability for Alzheimer’s disease. Ancestry-associated DEGs also show general enrichment for the heritability of diverse immune-related traits but depletion for psychiatric-related traits. We also compared Black and non-Hispanic white Americans, confirming most ancestry-associated DEGs. Our results delineate the extent to which genetic ancestry affects differences in gene expression in the human brain and the implications for brain illness risk.

DOI: 10.1038/s41593-024-01636-0

Source: https://www.nature.com/articles/s41593-024-01636-0