Polygenic Risk Scores in Clinical Schizophrenia Research

摘要

Most general population risk for schizophrenia is accounted for by common variations in the genome, but each variant explains only a tiny fraction of increased risk. In contrast, approximately 1%—2% of individuals with the diagnosis of schizophrenia have a microstructural chromosomal abnormality resulting in either a deletion or duplication of a segment of the genome, typically involving more than 100,000 nucleotides and many genes. These so-called copy number variations (CNVs) typically arise during meiosis and are found on one parental chromosome. They tend to be much more clinically penetrant than common variants, presumably because they involve a dosage alteration of genes within the CNV region, although they account for much less population risk. Close to a dozen CNVs have been associated with the diagnosis of schizophrenia, and as with common variants, they span the genome and do not converge on a simple common biology. Although the more penetrant schizophrenia associated CNVs are of potential value in genetic counseling, and some involve a high probability of intellectual compromise, none are more likely to result in the diagnosis of schizophrenia than not.