Summary statistics of risk loci for all-cause dementia, AD and VD in T2D

Dementia, a critical complication of type 2 diabetes (T2D), presents significant challenges due to its poor prognosis. Despite the importance of determining the genetic background underlying diabetic complications, limited knowledge is available for T2D-related dementia. To address this knowledge gap, we conducted genome-wide association studies in 39,574 T2D participants from the UK Biobank. Risk variants and risk genes exclusive to T2D-related dementia were identified, implicating additional mechanisms for proteinopathy and disrupted lipid metabolism. Functional genomic analysis further highlighted the key roles of glucose, cholesterol metabolism, and type 2 immune dysfunction in T2D-related dementia pathogenesis. The genetic risk of T2D-related dementia was also specifically enriched in pan-limbic system structures and neurons. Based on this specific genetic background, a polygenic score was further tailored for dementia risk stratification in patients with T2D. These findings provide insights into the genetic basis of T2D-related dementia and highlight potential pathways for mechanistic investigation and diagnostics.This dataset contains all summary statistics generated during the process.痴呆作为2型糖尿病（type 2 diabetes, T2D）的严重并发症，因其预后不佳而带来了诸多临床挑战。尽管明确糖尿病并发症的遗传背景至关重要，但目前学界对2型糖尿病相关痴呆的认知仍较为匮乏。为填补这一研究空白，我们针对英国生物银行（UK Biobank）中的39574名2型糖尿病参与者开展了全基因组关联研究（genome-wide association studies）。本研究识别出了2型糖尿病相关痴呆特有的风险变异与风险基因，提示了蛋白质病（proteinopathy）与脂质代谢紊乱的额外致病通路。功能基因组学分析（functional genomic analysis）进一步揭示了葡萄糖代谢、胆固醇代谢以及2型免疫功能异常在2型糖尿病相关痴呆发病机制中的关键作用。2型糖尿病相关痴呆的遗传风险还特异性富集于泛边缘系统结构与神经元内。基于这一特定遗传背景，我们进一步定制了用于2型糖尿病患者痴呆风险分层的多基因评分（polygenic score）。本研究结果为2型糖尿病相关痴呆的遗传基础提供了新见解，并为机制研究与诊断开发指明了潜在通路。本数据集涵盖了本研究分析全过程中生成的全部汇总统计量（summary statistics）。