36680483 - Genes, Brain and Behavior (2009) 8: 238247 #...

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Unformatted text preview: Genes, Brain and Behavior (2009) 8: 238247 # 2009 The Authors Journal compilation # 2009 Blackwell Publishing Ltd/International Behavioural and Neural Genetics Society Replication study of candidate genes for cognitive abilities: the Lothian Birth Cohort 1936 L. M. Houlihan , S. E. Harris , M. Luciano , A. J. Gow , J. M. Starr , P. M. Visscher and I. J. Deary* , Centre for Cognitive Ageing and Cognitive Epidemiology, Depart- ment of Psychology and Department of Geriatric Medicine, University of Edinburgh, Edinburgh, UK, and Queensland Statis- tical Genetics, Queensland Institute of Medical Research, Bris- bane, Australia *Corresponding author: I. J. Deary, Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK. E-mail: i.deary@ed.ac.uk As the proportion of older people in societies has increased, research into the determinants of cognitive ageing has risen in importance. Genetic influences account for over 50% of the variance in adult cognitive abilities. Previous studies on cognition and illnesses with cognitive impairments have identified single nucleotide polymorphisms ( SNPs) within candidate genes that might influence cognition or age-related cognitive change. This study investigated 10 candidate genes in over 1000 Scots: the Lothian Birth Cohort 1936 (LBC1936). These participants were tested on general cognitive ability (Scottish Mental Survey 1947) at age 11. At mean age 70, they completed the same general cognitive ability test and a battery of diverse cognitive tests. Nineteen SNPs in 10 genes previously associated with cognition, Alzheimers disease or autism were genotyped in 1063 individuals. The genes include BDNF, COMT, DISC1, KL, NCSTN, PPP1R1B, PRNP, SHANK3, SORL1 and WRN . Linear regression analysis investigated the additive effect of each SNP on the cognitive variables, covarying for gender and age. Childhood cognitive ability was also included as a covariate to identify associations specifically with cognitive ageing. Certain SNPs reached the conventional significance threshold for association with cognitive traits or cognitive ageing in LBC1936 ( P < 0.05). No SNPs reached the Bonferroni-level of significance (all P > 0.0015). Of the 10 genes, we discuss that COMT , KL , PRNP, PPP1R1B, SORL1 and WRN espe- cially merit further attention for association with cogni- tive ability and/or age-related cognitive change. All results are also presented so that they are valuable for future meta-analyses of candidate genes for cognition. Keywords: Cognition, candidate genes, Lothian Birth Cohort 1936, replication study Received 22 October 2008, revised 10 November 2008, accepted for publication 11 November 2008 Introduction Cognitive ability is an important predictor of life outcomes, especially in old age. Additive genetic effects account for over 50% of the variance in cognitive ability from adolescence...
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36680483 - Genes, Brain and Behavior (2009) 8: 238247 #...

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