Houlihan L M, Harris S E, Luciano M, Gow A J, Starr J M, Visscher P M, Deary I J
Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, UK.
Genes Brain Behav. 2009 Mar;8(2):238-47. doi: 10.1111/j.1601-183X.2008.00470.x. Epub 2008 Dec 10.
As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms (SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimer's disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN. Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 (P < 0.05). No SNPs reached the Bonferroni-level of significance (all P > 0.0015). Of the 10 genes, we discuss that COMT, KL, PRNP, PPP1R1B, SORL1 and WRN especially merit further attention for association with cognitive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition.
随着社会中老年人比例的增加，对认知衰老决定因素的研究变得越发重要。基因影响在成人认知能力的差异中占比超过50%。先前关于认知和认知障碍疾病的研究已经在可能影响认知或与年龄相关的认知变化的候选基因中鉴定出单核苷酸多态性（SNP）。本研究在1000多名苏格兰人中调查了10个候选基因：1936年洛锡安出生队列（LBC1936）。这些参与者在11岁时接受了一般认知能力测试（1947年苏格兰智力调查）。在平均年龄70岁时，他们完成了相同的一般认知能力测试和一系列不同的认知测试。对1063名个体的10个先前与认知、阿尔茨海默病或自闭症相关的基因中的19个SNP进行了基因分型。这些基因包括BDNF、COMT、DISC1、KL、NCSTN、PPP1R1B、PRNP、SHANK3、SORL1和WRN。线性回归分析研究了每个SNP对认知变量的加性效应，并对性别和年龄进行了协变量调整。童年认知能力也作为协变量纳入，以确定与认知衰老的特定关联。在LBC1936中，某些SNP达到了与认知特征或认知衰老相关的传统显著性阈值（P < 0.05）。没有SNP达到邦费罗尼显著性水平（所有P > 0.0015）。在这10个基因中，我们讨论认为COMT、KL、PRNP、PPP1R1B、SORL1和WRN与认知能力和/或与年龄相关的认知变化的关联尤其值得进一步关注。所有结果也都呈现出来，以便它们对未来认知候选基因的荟萃分析有价值。
