共享的遗传和神经免疫结构将1型糖尿病与神经认知特征联系起来
Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits.
摘要(中文译文)
1型糖尿病，尤其是儿童期发病者，与神经认知特征改变相关，但其潜在的生物学机制尚不清楚。在此，我们将全基因组关联分析结果与单细胞表观基因组图谱进行整合，发现1型糖尿病遗传力富集于人脑驻留细胞的可及染色质区域，其中最显著的是小胶质细胞，且这一现象贯穿神经发育至成年期。经Bonferroni校正的跨性状遗传相关分析显示，1型糖尿病与智力、执行功能和双相情感障碍呈负相关，与重症肌无力呈正相关。联合错误发现率分析识别出同时影响1型糖尿病和神经认知特征的多效性位点，包括17q21.31神经基因组枢纽区域。孟德尔随机化进一步表明，教育程度、智力、阿尔茨海默病和双相情感障碍对1型糖尿病风险具有保护作用，而多发性硬化和重症肌无力的遗传易感性则增加1型糖尿病风险。在反向方向上，1型糖尿病的遗传易感性与重症肌无力风险增加相关。我们在脑和免疫细胞中识别出若干同时影响1型糖尿病和神经认知特征的基因表达调控变异，其中一些在疾病受累组织与对照组织之间表现出方向一致的差异表达。总之，这些发现凸显了连接1型糖尿病与认知及神经精神疾病风险的多效性遗传和神经免疫机制。
Abstract
Type 1 diabetes, particularly with childhood onset, is associated with altered neurocognitive traits, yet the underlying biological mechanisms are unclear. Here, we integrate genome-wide association results with single-cell epigenomic profiles and show that type 1 diabetes heritability is enriched in accessible chromatin of human brain-resident cells, most notably microglia, across neurodevelopment into adulthood. Bonferroni-corrected cross-trait genetic correlation analyses reveal negative correlations of type 1 diabetes with intelligence, executive function, and bipolar disorder, and a positive correlation with myasthenia gravis. Conjunctional false discovery rate analysis identifies pleiotropic loci jointly influencing type 1 diabetes and neurocognitive traits, including the 17q21.31 neurogenomic hub. Mendelian randomization further demonstrates protective effects of educational attainment, intelligence, Alzheimer's disease, and bipolar disorder on type 1 diabetes risk, whereas liability to multiple sclerosis and myasthenia gravis increases type 1 diabetes risk. In the reverse direction, liability to type 1 diabetes is associated with increased risk of myasthenia gravis. We identify several gene expression regulatory variants in brain and immune cells that jointly influence type 1 diabetes and neurocognitive traits, some of which show concordant differential expression in disease-affected versus control tissue. Together, these findings highlight pleiotropic genetic and neuroimmune mechanisms that link type 1 diabetes with cognition and neuropsychiatric disease risk.
如何引用
AMA
Priscilla Saarah, Zehra A Syeda, Ziang Xu, Yikai Dong, Habei Jiang, Michelle Shanguhyia, et al. Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits.. Nature communications. 2026; doi:10.1038/s41467-026-70694-8.
APA
Priscilla Saarah, Zehra A Syeda, Ziang Xu, Yikai Dong, Habei Jiang, Michelle Shanguhyia, et al (2026). Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits.. Nature communications. https://doi.org/10.1038/s41467-026-70694-8
GB/T 7714
Priscilla Saarah, Zehra A Syeda, Ziang Xu, Yikai Dong, Habei Jiang, Michelle Shanguhyia, et al. Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits.[J]. Nature communications, 2026 doi:10.1038/s41467-026-70694-8.
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