title: Genetic effects on information processing speed are moderated by age--converging results from three samples.
abstract: Information processing is a cognitive trait forming the basis of complex abilities like executive function. The Trail Making Test (TMT) is a well-established test of information processing with moderate to high heritability. Age of the individual also plays an important role. A number of genetic association studies with the TMT have been performed, which, however, did not consider age as a moderating factor. We report the results of genome-wide association studies (GWASs) on age-independent and age-dependent TMT performance in two population-representative community samples (Munich Antidepressant Response Signature, MARS: N1 = 540; Ludwig Maximilians University, LMU: N2 = 350). Age-dependent genome-wide findings were then evaluated in a third sample of healthy elderly subjects (Sydney Memory and Ageing Study, Sydney MAS: N3 = 448). While a meta-analysis on the GWAS findings did not reveal age-independent TMT associations withstanding correction for multiple testing, we found a genome-wide significant age-moderated effect between variants in the DSG1 gene region and TMT-A performance predominantly reflecting visual processing speed (rs2199301, P(meta-analysis) = 1.3 × 10(-7)). The direction of the interaction suggests for the minor allele a beneficial effect in younger adults turning into a detrimental effect in older adults. The detrimental effect of the missense single nucleotide polymorphism rs1426310 within the same DSG1 gene region could be replicated in Sydney MAS participants aged 70-79, but not in those aged 80 years and older, presumably a result of survivor bias. Our findings demonstrate opposing effects of DSG1 variants on information processing speed depending on age, which might be related to the complex processes that DSG1 is involved with, including cell adhesion and apoptosis.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ising
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: K A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Zimmermann
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Brückl
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Höhne
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.|Present address: Institute of Psychology, University of Basel, Basel, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Heck
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.|Present address: Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: L A
authors.initials: LA
authors.lastname: Schenk
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Martin-Luther-University, Halle, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Rujescu
authors.affiliation: School of Mathematics and Statistics, University of Sydney.
authors.forename: N J
authors.initials: NJ
authors.lastname: Armstrong
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, The University of New South Wales, Sydney, Australia.|Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, Australia.
authors.forename: P S
authors.initials: PS
authors.lastname: Sachdev
authors.affiliation: Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Medicine, The University of New South Wales, Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Reppermund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology; D051183:Desmoglein 1 / Q000235:genetics; D056344:Executive Function; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C495297:DSG1 protein, human; D051183:Desmoglein 1
keywords: Age; DSG1; GWAS; Trail Making Test; information processing; processing speed