Number of Genes Associated with Neuroticism due to Their Polymorphisms

Neuroticism is a personality trait, which is an important risk factor for psychiatric disorders. Recent genome-wide studies have reported about 600 genes potentially influencing neuroticism. This list consists of both genes whose polymorphisms directly regulate the level of neuroticism and genes whose expression is controlled by genetic variants outside the gene. The first group of genes is more interesting because within-gene association signals are usually easy to interpret and less probable to be false positives. We analyzed and compared the results of two published studies to estimate the number of such genes in the list of neuroticism genes. We demonstrated that 98 known genes were associated with neuroticism owing to their polymorphisms and 134 genes were associated with neuroticism owing to the genetic variants outside the gene. For the remaining genes, we estimated the chance to be in the first group. As a result, according to our estimates, only from 153 to 198 genes of almost 600 known neuroticism genes affect the trait owing to their within-gene polymorphisms. Thus, using neuroticism as an example, we demonstrated that only 25–33% of the genes identified by the widely used methods control the trait by the within-gene variation. This estimate predicts the effectiveness of the whole exome sequencing to increase the power of association analysis.