An Experimental Study on the Influence of Friends and Popular Peers on Adolescents' Risky Decisions in a Private and Public Context.

Schizophrenia stands as one of the most disabling human brain disorders in adults, usually requiring lifelong treatment []. Among known genetic forms of schizophrenia (mostly copy number variation (CNV)-related), the 22q11.2 deletion confers the highest risk of developing schizophrenia and thus represents a unique genetic model for studying this serious psychotic illness [–]. One in every four individuals born with a 22q11.2 deletion develops schizophrenia, 25 times greater than the general population risk []. This deletion is present in about 1% of patients with schizophrenia and is one of the most recurrent CNVs, occurring in nearly 1 in 2000 live births, usually as a de novo event, causing 22q11.2 deletion syndrome (22q11.2DS) [–]. Although placing individuals at markedly high risk, the majority of individuals with a 22q11.2 deletion do not develop schizophrenia. The clinical features of schizophrenia caused by the 22q11.2 microdeletion appear indistinguishable from other forms of schizophrenia [, ], and available data so far indicate that the additional genetic variants contributing to schizophrenia risk are the same as those that contribute to schizophrenia risk in the general population [, ], suggesting that individuals with 22q11.2 deletions represent a valuable population for understanding the causes of schizophrenia, and the reduced penetrance and variable expressivity that is characteristic of all schizophrenia-associated genetic variants discovered to date [, , –]. Schizophrenia is well-known for its polygenic nature, where multiple genetic variants contribute to its genetic risk. Previously, we and others have shown that the aggregate effect of common risk alleles and additional rare copy number variants (CNVs) in the genome can affect the penetrance of schizophrenia in individuals with a 22q11.2 deletion [, ]. Rare nonsynonymous variants affecting genes involved in cortical development have also been shown to increase risk of schizophrenia in this context [, ]. However, these effects are not large enough to allow differentiation of individuals with and without schizophrenia, suggesting that other major modifying factors beyond the high risk imparted by the 22q11.2 deletion remain to be identified. This is a goal of both scientific and clinical interest [, , ]. In recent studies, we have determined that tandem repeats, which constitute ~8% of the human genome, contribute to schizophrenia risk when they are expanded [, ]. These repeats tend to be located within or near genes known to be implicated in schizophrenia, e.g., from genome-wide association studies []. Schizophrenia studies that excluded individuals with 22q11.2 deletions showed a differential presence of rare tandem repeat expansions (TREs) in individuals with and without other schizophrenia-associated CNVs of lower penetrance, e.g., 16p11.2 duplication []. We therefore proposed to determine whether TREs could be a significant genetic modifier for schizophrenia in the presence of a high-risk 22q11.2 deletion, and to examine potential molecular mechanisms of disease.