title: Evolutionary conserved longevity genes and human cognitive abilities in elderly cohorts.
abstract: 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.
authors: Department of Psychology, The University of Edinburgh, Edinburgh, UK. lorna.lopez@ed.ac.uk
authors: Lorna M
authors: LM
authors: Lopez
authors: Sarah E
authors: SE
authors: Harris
authors: Michelle
authors: M
authors: Luciano
authors: Dave
authors: D
authors: Liewald
authors: Gail
authors: G
authors: Davies
authors: Alan J
authors: AJ
authors: Gow
authors: Albert
authors: A
authors: Tenesa
authors: Antony
authors: A
authors: Payton
authors: Xiayi
authors: X
authors: Ke
authors: Lawrence J
authors: LJ
authors: Whalley
authors: Helen
authors: H
authors: Fox
authors: Paul
authors: P
authors: Haggerty
authors: William
authors: W
authors: Ollier
authors: Andrew
authors: A
authors: Pickles
authors: David J
authors: DJ
authors: Porteous
authors: Michael A
authors: MA
authors: Horan
authors: Neil
authors: N
authors: Pendleton
authors: John M
authors: JM
authors: Starr
authors: Ian J
authors: IJ
authors: Deary
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D015331:Cohort Studies; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008568:Memory; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D009419:Nerve Tissue Proteins; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases