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Neurocognitive impairment in type 2 diabetes: evidence for shared genetic aetiology.
Diabetologia ( IF 8.4 ) Pub Date : 2020-02-04 , DOI: 10.1007/s00125-020-05101-y
Josephine Mollon 1 , Joanne E Curran 2, 3 , Samuel R Mathias 1 , Emma E M Knowles 1 , Phoebe Carlisle 4 , Peter T Fox 5 , Rene L Olvera 5, 6 , Harald H H Göring 2, 3 , Amanda Rodrigue 1 , Laura Almasy 7 , Ravi Duggirala 2, 3 , John Blangero 2, 3 , David C Glahn 1, 4
Affiliation  

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:


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。
更新日期:2020-04-22
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