Heritability and genetic association analysis of cognition in the Diabetes Heart Study.
Heritability and genetic association analysis of cognition in the Diabetes Heart Study.
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DOI：
10.1016/j.neurobiolaging.2014.03.005
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发表时间：
2014-08
影响因子：
4.2
通讯作者：
Bowden DW
中科院分区：
文献类型：
--
作者：
Cox AJ;Hugenschmidt CE;Raffield LM;Langefeld CD;Freedman BI;Williamson JD;Hsu FC;Bowden DW
认知能力是健康老龄化的重要组成部分。2型糖尿病（T2 D）与大脑和认知的负面结果有关，尽管因果机制尚未明确确定。在这方面，遗传风险因素值得进一步考虑。本研究采用（1）数字符号替代任务、（2）改良简易智力状态测验、（3）Stroop任务、（4）Rey听觉-言语学习任务、（5）听觉-言语学习任务、（6）听觉-言语学习任务、（7）听觉-言语学习任务、（8）听觉-言语学习任务、（9）听觉-言语学习任务、（10）听觉-言语和（5）控制性口语词汇联想任务的语音和语义流畅性，在家庭为基础的，T2 D丰富，糖尿病心脏研究样本（来自257个家庭的550名参与者）。通过与候选单核苷酸多态性（SNP）和全基因组SNP数据的关联分析，进一步评估这些认知指标的遗传基础。在调整年龄、性别和教育后，认知功能的测量结果具有显著的遗传性（ε 2 = 0.28-0.62）。当应用保守的显著性度量时，选择形成候选SNP的先验集合的总共31个SNP（来自26个基因/区域）显示出与认知功能关联的有限证据。对非编码和编码变体的全基因组评估显示了几种编码变体之间存在关联的证据，包括CNST中的rs 139509083（p = 4.9 × 10−9），PLAA中的rs 199968569（p = 4.9 × 10−9）和PCDH 8中的rs 138487371（p = 3.7 × 10−8）。T2 D中认知表现的遗传成分的鉴定表明，即使在存在代谢疾病和其他相关合并症的情况下，遗传因素对认知表现也有作用，并且在功能上合理的候选人中鉴定遗传相关信号也支持这一点。
Cognitive performance is an important component of healthy aging. Type 2 diabetes (T2D) is associated with negative outcomes for the brain and cognition, although causal mechanisms have not been definitely determined. Genetic risk factors warrant further consideration in this context. This study examined the heritability of cognitive function as assessed by (1) the Digit Symbol Substitution Task; (2) the Modified Mini-Mental State Examination; (3) the Stroop Task; (4) the Rey Auditory-Verbal Learning Task; and (5) the Controlled Oral Word Association Task for Phonemic and Semantic Fluency, in the family-based, T2D-enriched, Diabetes Heart Study sample (n = 550 participants from 257 families). The genetic basis of these cognitive measures was further evaluated by association analysis with candidate single-nucleotide polymorphisms (SNPs) and genome-wide SNP data. Measures of cognitive function were significantly heritable (ĥ2 = 0.28–0.62) following adjustment for age, gender, and education. A total of 31 SNPs (from 26 genes/regions) selected to form an a priori set of candidate SNPs showed limited evidence of association with cognitive function when applying conservative metrics of significance. Genome-wide assessment of both noncoding and coding variants revealed suggestive evidence of association for several coding variants including rs139509083 in CNST (p = 4.9 × 10−9), rs199968569 in PLAA (p = 4.9 × 10−9) and rs138487371 in PCDH8 (p = 3.7 × 10−8). The identification of a heritable component to cognitive performance in T2D suggests a role for genetic contributors to cognitive performance even in the presence of metabolic disease and other associated comorbidities and is supported by the identification of genetic association signals in functionally plausible candidates.
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影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
5.2
作者：
Cirulli, Elizabeth T.;Kasperaviciute, Dalia;Goldstein, David B.
通讯作者：
Goldstein, David B.
DOI：
10.1038/oby.2005.42
发表时间：
2005-02-01
期刊：
OBESITY RESEARCH
影响因子：
--
作者：
Hsu, FC;Lenchik, L;Carr, JJ
通讯作者：
Carr, JJ
DOI：
10.1073/pnas.021506298
发表时间：
2001-01-16
影响因子：
11.1
作者：
Buetow, KH;Edmonson, M;Braun, A
通讯作者：
Braun, A
影响因子：
1.8
作者：
HOUX, PJ;JOLLES, J;VREELING, FW
通讯作者：
VREELING, FW