Department of Psychology, The University of Edinburgh, Edinburgh, UK.
Eur J Hum Genet. 2012 Mar;20(3):341-7. doi: 10.1038/ejhg.2011.201. Epub 2011 Nov 2.
Genetic influences have an important role in the ageing process. The genetic factors that influence success in bodily ageing may also contribute to the successful ageing of cognitive abilities. A comparative genomics approach found longevity genes conserved between yeast Saccharomyces cerevisiae and nematode Caenorhabditis elegans. We hypothesised that these longevity genes influence variance in cognitive ability and age-related cognitive decline in humans. Here, we investigated six of these genes that have human orthologs and show expression in the brain. We tested AFG3L2 (MIM: 604581, AFG3 ATPase family gene 3-like 2 (yeast)), FRAP1 (MIM: 601231, a FK506 binding protein 12-rapamycin associated protein), MAT1A, MAT2A (MIM: 610550 and 601468, methionine adenosyltransferases I alpha and II alpha, respectively), SYNJ1 and SYNJ2 (MIM: 604297 and 609410, synaptojanin-1 and synaptojanin-2, respectively) in approximately 1000 healthy older Scots: the Lothian Birth Cohort 1936 (LBC1936). They were tested on general cognitive ability at age 11 years. At a mean age of 70 years, they re-sat the same general cognitive ability test and underwent an additional battery of diverse cognitive tests. In all, 70 tag and functional SNPs in the six longevity genes were genotyped and tested for association with cognition and cognitive ageing in LBC1936. Suggestive associations were detected between SNPs in SYNJ2, MAT1A, AFG3L2 and SYNJ1 and a general memory factor and general cognitive ability at age 11 and 70 years. Replication studies for cognitive ability associations were performed in 2506 samples from the Cognitive Ageing Genetics in England and Scotland consortium. A meta-analysis replicated the SYNJ2 association with cognitive abilities (lowest P=0.00077). SYNJ2 is a novel gene in which variation is potentially associated with cognitive abilities.
遗传因素在衰老过程中起着重要作用。影响身体衰老成功的遗传因素也可能有助于认知能力的成功衰老。比较基因组学方法发现，酵母酿酒酵母和线虫秀丽隐杆线虫之间存在长寿基因。我们假设这些长寿基因影响人类认知能力的差异和与年龄相关的认知能力下降。在这里，我们研究了其中六个具有人类同源物且在大脑中表达的基因。我们测试了 AFG3L2（MIM：604581，AFG3 ATPase 家族基因 3 样 2（酵母））、FRAP1（MIM：601231，FK506 结合蛋白 12-雷帕霉素相关蛋白）、MAT1A、MAT2A（MIM：610550 和 601468，分别为蛋氨酸腺苷转移酶 Iα和 IIα）、SYNJ1 和 SYNJ2（MIM：604297 和 609410，突触结合蛋白-1 和突触结合蛋白-2）在大约 1000 名健康的苏格兰老年人中：洛锡安 1936 年出生队列（LBC1936）。他们在 11 岁时接受了一般认知能力测试。在平均年龄为 70 岁时，他们重新参加了相同的一般认知能力测试，并接受了额外的多种认知测试。总共在六个长寿基因中的 70 个标记和功能 SNP 进行了基因分型，并测试了它们与 LBC1936 认知和认知衰老的关联。在 SYNJ2、MAT1A、AFG3L2 和 SYNJ1 的 SNP 与 11 岁和 70 岁时的一般记忆因子和一般认知能力之间检测到了提示性关联。在英格兰和苏格兰认知老化遗传学联盟的 2506 个样本中进行了认知能力关联的复制研究。对认知能力关联的荟萃分析复制了 SYNJ2 与认知能力的关联（最低 P=0.00077）。SYNJ2 是一个新基因，其变异可能与认知能力有关。
