Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Shared genetic and neuroimmune architecture links type 1 diabetes with neurocognitive traits

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月13日

查看全文
  • Priscilla Saarah,
  • Zehra A. Syeda,
  • Ziang Xu,
  • Yikai Dong,
  • Habei Jiang,
  • Michelle Shanguhyia,
  • Sourav Roy,
  • Biqing Zhu,
  • Le Zhang,
  • Andrew T. Dewan,
  • Samira Asgari,
  • David A. Alagpulinsa

摘要

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.