Variation in the dysbindin gene and normal cognitive function in three independent population samples |
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Authors: | M. Luciano F. Miyajima P. A. Lind T. C. Bates M. Horan S. E. Harris M. J. Wright W. E. Ollier C. Hayward N. Pendleton A. J. Gow P. M. Visscher J. M. Starr I. J. Deary N. G. Martin and A. Payton |
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Affiliation: | Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh;, and Centre for Integrated Genomic Medical Research, The University of Manchester, Manchester, UK;, Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia;, Clinical Gerontology, The University of Manchester, Salford, Greater Manchester;, Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh;, and Department of Geriatric Medicine, University of Edinburgh, Royal Victoria Hospital, Edinburgh, UK |
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Abstract: | The association between DTNBP1 genotype and cognitive abilities was investigated in three population samples (1054 Scottish, 1806 Australian and 745 English) of varying age. There was evidence in each of the cohorts for association ( P < 0.05) to single nucleotide polymorphisms ( SNPs) and haplotypes previously shown to relate to cognition. By comparison with previous findings, these associations included measures of memory, and there was at best equivocal evidence of association with general cognitive ability. Of the SNPs typed in all three cohorts, rs2619528 and rs1011313 showed significant association with measures of executive function in two cohorts, rs1018381 showed significant association with verbal ability in one cohort and rs2619522 showed significance/marginal significance with tests of memory, speed and executive function in two cohorts. For all these SNPs, the direction and magnitude of the allelic effects were consistent between cohorts and with previous findings. In the English cohort, a previously untested SNP (rs742105) located in a distinct haplotype block upstream of the other SNPs showed the strongest significance ( P < 0.01) for measures of memory but weaker significance for general cognitive ability. Our results therefore support involvement of the dysbindin gene in cognitive function, but further work is needed to clarify the specific functional variants involved and the cognitive abilities with which they are associated. |
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Keywords: | Cognitive ability DTNBP1 haplotypes memory normal population |
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