title: Cognitive ability, intraindividual variability, and common genetic variants of catechol-O-methyltransferase and brain-derived neurotrophic factor: a longitudinal study in a population-based sample of older adults.
abstract: Genetic differences play a significant role in generating individual differences in cognitive abilities. Studies have linked common polymorphisms (valine to methionine substitution; VAL/MET) in the catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) to cognitive differences between individuals. However, not all studies support these associations and hence, the impact of these polymorphisms on cognition is unclear. Here, we investigated the effect of COMT VAL158MET and BDNF VAL66MET polymorphisms and their interaction on cognitive performance measured longitudinally over 8 years in a population-based sample of older adults (60-64 years at baseline; n = 400). We used multilevel models to examine differences between individuals with different genotypes in performance on psychometric tests while controlling for age, sex, and education. We observed significant main and interaction effects of COMT and BDNF genotypes on reaction time (RT) and intraindividual variability in RT (IIV-RT). Subjects with at least one copy of the COMT*MET allele (which is associated with higher prefrontal dopamine) had significantly faster RT (both simple and choice RT) and less IIV-RT in both tasks than those without the COMT*MET allele when they also carried one or more BDNF*MET alleles (which is associated with lower activity-dependent BDNF secretion). However, RT and IIV-RT did not differ significantly between the COMT genotypes in the absence of the BDNF*MET allele. These polymorphisms had no significant effect on within person change in RT or IIV-RT. Our findings indicate that the interaction between common variants of COMT and BDNF explain individual differences in RT and IIV-RT but do not explain age-related decline in these abilities.
authors: Department of Genome Biology, John Curtin School of Medical Research, Australian National University.
authors: Debjani
authors: D
authors: Das
authors: Department of Genome Biology, John Curtin School of Medical Research, Australian National University.
authors: Xiaoyun
authors: X
authors: Tan
authors: Department of Human Development and Family Studies, Colorado State University.
authors: Allison A M
authors: AA
authors: Bielak
authors: Centre for Research on Ageing, Health and Wellbeing.
authors: Nicolas
authors: N
authors: Cherbuin
authors: Department of Genome Biology, John Curtin School of Medical Research, Australian National University.
authors: Simon
authors: S
authors: Easteal
authors: Centre for Research on Ageing, Health and Wellbeing.
authors: Kaarin J
authors: KJ
authors: Anstey
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000502:physiology / Q000523:psychology*; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007206:Individuality; D008137:Longitudinal Studies; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine