Genes Affecting Cognitive and Emotional Functions

Abstract

With the exception of comparatively rare single gene disorders causing mental handicap or acquired cognitive decline later in life, the genetic basis of cognitive and emotional function is complex. There is overwhelming evidence from the studies of families, twins and adoptees that cognitive ability, as measured for example by IQ tests, at least 50 % heritable. Similarly, studies of emotionality in twins, as indexed by measures of personality within the normal range or occurrence of clinical depression, show greater similarity in monozygotic than dizygotic pairs, indicating a genetic component. However, the fact that monozygotic twins are not identical with respect to cognitive ability or emotional status demonstrates that environmental factors are also at work. This, together with the likelihood that there are several or perhaps many genes influencing cognition or emotional functions, means that each gene on its own will have a comparatively small effect. Hence, locating and identifying the relevant genes are far more difficult tasks than for single-gene traits or disorders. Although work on laboratory-bred animals has produced some interesting preliminary results in detecting quantitative trait loci (QTLs), rodent models of emotionality or cognitive ability are relatively crude and cannot do justice to the complexity of human behaviours. Current attempts to identify genes have largely focused on variations at candidate loci, for example, genes relevant to a serotonergic pathways, and have mainly used allelic association, an approach capable of detecting genes of small effect. However, there is increasing interest in attempting whole genome searches looking for linkage disequilibrium. Because linkage disequilibrium is usually only found over small distances (1 centimorgan or less), this approach involves an enormous amount of genotyping. In an attempt to overcome this difficulty we have developed a DNA pooling method as a means of rapidly scanning whole chromosomes. Some promising data using this method on a study of cognitive ability will be discussed.