Pity the little boy who would like to join others in building a structure out of Lego blocks, yet who doesn’t trust himself to do so. He can undoubtedly blame his feelings, at least in part, on his genes.

The reason? Israeli scientists have linked shyness in children with the inheritance of a particular gene variant. The finding was published in the April American Journal of Psychiatry.

Shoshana Arbelle, M.D., a lecturer in health sciences at Ben-Gurion University’s Soroka Medical Center, Richard Ebstein, Ph.D., a professor of psychology at Hebrew University, and coworkers assessed shyness in some 100 second-grade children, using a composite scale derived from questionnaires given not just to the children, but to their parents and teachers. They found significant correlations between the ratings of the children, parents, and teachers concerning which children were shy and which were not.

The researchers then took DNA samples from the children and examined them for the presence of variants of four genes that are "hot" in human behavioral genetic studies these days. They are the 5-HTTLPR gene (for serotonin transporter promoter region 44 base pair insertion/deletion), DRD4 gene (for dopamine D4 receptor exon III repeat), COMT gene (for catechol O-methyltransferase), and MAO A gene (for monoamine oxidase A promoter region repeat).

The scientists then looked to see whether they could make a statistically significant link between subjects with high shyness scores and the possession of various variants of these four genes. They could for one variant of the 5-HTTLPR gene, but not for the other variants.

This finding is probably not surprising. The variant of the 5-HTTLPR gene that they connected with shyness has also been found in the past to be implicated in anxiety.

The finding has drawn a comment from the co-discoverer of the double-helical structure of DNA, Nobel laureate James Watson. The April American Journal of Psychiatry commemorated the 50th anniversary of the discovery of the double helix, and Watson provided a commentary in the issue. In this commentary, he wrote that he and co-discoverer Francis Crick realized that theirs was a "pivotal discovery" when they published it in Nature in 1953. Yet they had no idea, Watson admitted, "what richness" would flow from it in ensuing years. And one example, he pointed out, is this finding of what appears to be a shyness gene for children.

The study was financed by the Israel Ministry of Health and the Israel Science Foundation.

The study, "Relation of Shyness in Grade School Children to the Genotype for the Long Form of the Serotonin Transporter Promoter Region Polymorphism," is posted on the Web at http://ajp.psychiatryonline.org/cgi/content/full/160/4/671?. ▪

Am J Psychiatry  2003160671