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Exploring candidate gene associations with neuropsychological performance
Author(s) -
McQueen Matthew B.,
Bertram Lars,
Lange Christoph,
Becker K.D.,
Albert Marilyn S.,
Tanzi Rudolph E.,
Blacker Deborah
Publication year - 2007
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30500
Subject(s) - neuropsychology , apolipoprotein e , cognition , psychology , neuropsychological test , genetic association , longitudinal study , alzheimer's disease , cohort , disease , association (psychology) , phenotype , clinical psychology , gene , medicine , biology , genetics , neuroscience , genotype , single nucleotide polymorphism , pathology , psychotherapist
Abstract We hypothesize that quantitative phenotypes related to Alzheimer's disease (AD), rather than the dichotomous disease phenotype, will increase the statistical power for identifying genetic risk factors. Neuropsychological test scores, which allow for the measurement of loss of cognitive function over time, are a particularly promising option for this approach. Using data from a cohort study of prodromal AD in 365 community‐recruited subjects with and without memory problems with a baseline and often one or more follow‐up administrations of a detailed neuropsychological test battery, we performed both cross‐sectional and longitudinal analyses using the known AD gene APOE and four other putative AD genes as predictors. APOE and a promoter polymorphism in insulin degrading enzyme ( IDE_4U ) showed evidence for association with cross‐sectional and longitudinal changes in memory ( P = 0.016–0.025) and other cognitive functions. APOE and a polymorphism in the alpha‐2‐macroglobulin gene ( A2M18i ) also showed evidence for association with cross‐sectional and longitudinal changes in executive functioning ( P = 0.010–0.042). In some cases, longitudinal analysis offered stronger evidence for association than could be seen cross‐sectionally. These preliminary results suggest that this approach has promised the development of a quantitative phenotype related to AD, but more elaborate methods will be required to address multiple comparisons issues in the setting of correlated data. © 2007 Wiley‐Liss, Inc.