AIMS/HYPOTHESIS Type 2 diabetes is associated with cognitive impairments, but it is unclear whether common genetic factors influence both type 2 diabetes risk and cognition. METHODS Using data from 1892 Mexican-American individuals from extended pedigrees, including 402 with type 2 diabetes, we examined possible pleiotropy between type 2 diabetes and cognitive functioning, as measured by a comprehensive neuropsychological test battery. RESULTS Negative phenotypic correlations (ρp) were observed between type 2 diabetes and measures of attention (Continuous Performance Test [CPT d']: ρp = -0.143, p = 0.001), verbal memory (California Verbal Learning Test [CVLT] recall: ρp = -0.111, p = 0.004) and face memory (Penn Face Memory Test [PFMT]: ρp = -0.127, p = 0.002; PFMT Delayed: ρp = -0.148, p = 2 × 10-4), replicating findings of cognitive impairment in type 2 diabetes. Negative genetic correlations (ρg) were also observed between type 2 diabetes and measures of attention (CPT d': ρg = -0.401, p = 0.001), working memory (digit span backward test: ρg = -0.380, p = 0.005), and face memory (PFMT: ρg = -0.476, p = 2 × 10-4; PFMT Delayed: ρg = -0.376, p = 0.005), suggesting that the same genetic factors underlying risk for type 2 diabetes also influence poor cognitive performance in these domains. Performance in these domains was also associated with type 2 diabetes risk using an endophenotype ranking value approach. Specifically, on measures of attention (CPT d': β = -0.219, p = 0.005), working memory (digit span backward: β = -0.326, p = 0.035), and face memory (PFMT: β = -0.171, p = 0.023; PFMT Delayed: β = -0.215, p = 0.005), individuals with type 2 diabetes showed the lowest performance, while unaffected/unrelated individuals showed the highest performance, and those related to an individual with type 2 diabetes performed at an intermediate level. CONCLUSIONS/INTERPRETATION These findings suggest that cognitive impairment may be a useful endophenotype of type 2 diabetes and, therefore, help to elucidate the pathophysiological underpinnings of this chronic disease. DATA AVAILABILITY The data analysed in this study is available in dbGaP: www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2.

中文翻译：

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2 型糖尿病的神经认知障碍：共同遗传病因学的证据。


目的/假设 2 型糖尿病与认知障碍相关，但尚不清楚常见的遗传因素是否影响 2 型糖尿病风险和认知。方法 使用 1892 名来自大谱系的墨西哥裔美国人（其中 402 名患有 2 型糖尿病）的数据，我们检查了 2 型糖尿病和认知功能之间可能的多效性，这是通过综合神经心理学测试组测量的。结果 2 型糖尿病与注意力测量（持续表现测试 [CPT d']：ρp = -0.143，p = 0.001）、言语记忆（加州言语学习测试 [CVLT] 回忆：ρp）之间观察到负表型相关性 (ρp) = -0.111，p = 0.004）和面部记忆（佩恩面部记忆测试 [PFMT]：ρp = -0.127，p = 0.002；PFMT 延迟：ρp = -0.148，p = 2 × 10-4），复制认知的结果2 型糖尿病的损害。还观察到 2 型糖尿病与注意力测量（CPT d'：ρg = -0.401，p = 0.001）、工作记忆（数字跨度向后测试：ρg = -0.380，p = 0.005）之间存在负遗传相关性（ρg），和面部记忆（PFMT：ρg = -0.476，p = 2 × 10-4；PFMT 延迟：ρg = -0.376，p = 0.005），表明潜在 2 型糖尿病风险的相同遗传因素也会影响认知表现不佳这些域。使用内表型排名值方法，这些领域的表现也与 2 型糖尿病风险相关。具体来说，关于注意力测量（CPT d'：β = -0.219，p = 0.005）、工作记忆（向后数字跨度：β = -0.326，p = 0.035）和面部记忆（PFMT：β = -0.171，p = 0.023；PFMT 延迟：β = -0.215，p = 0。005），患有 2 型糖尿病的个体表现出最低的表现，而未受影响/无关的个体表现出最高的表现，而与患有 2 型糖尿病的个体相关的个体则表现出中等水平。结论/解释这些发现表明认知障碍可能是 2 型糖尿病的一个有用的内表型，因此有助于阐明这种慢性疾病的病理生理学基础。数据可用性 本研究分析的数据可在 dbGaP 中获取：www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001215.v2.p2。