There are multiple types of genetic alterations that contribute to human variability.Single nucleotide polymorphisms (SNPs) are common variants of individual nucleotide sequence. Copy Number Variants (CNV) are a type of structural variant ( inherited or de novo) involving alterations in the number of copies of specific regions of DNA, which can either be deleted or duplicated. Clinical syndromes caused by known CNVs include velocardiofacial, Prader-Willi, and Smith-Magenis syndromes. Increased presence of CNVs has been seen in autism spectrum disorder (ASD), ADHD, and intellectual disability (ID), as well as schizophrenia. Risk from CNVs for neurodevelopmental and psychiatric disorders have been of good effect size.
Anita Thapar and Miriam Cooper from Cardiff University examines the field of CNVs in child psychiatric disorders and summarise what we know now.
1.CNV mutations can arise denovo and is associated with risk of ASD, ID, and schizophrenia but would not contribute to the familial transmission of these disorders.
2. Pleiotropy: Same CNV is associated with increased risk of different types of disorders: ie same genetic risks operate across diagnostic categories like Schizophrenia, ASD,ADHD, ID
3. CNV locations provide meaningful clues to the neurobiology of these disorders , for example, CNV studies of ASD, schizophrenia, and ID have strongly implicated disrupted synaptic function
4. It is difficult to prove causal pathogenic effects. mutiple risk factors work together.Inferring causality is further complicated by comorbidity.
5. Though screening for rare CNVs in idiopathic ID has become increasingly commonplace it seems unlikely that routine CNV testing will become established for the majority of individuals with psychiatric disorders unless they also have ID or multiple developmental morbidities.
For most complex disorders, one risk factor is neither necessary or sufficient. Many carriers of risk CNVs will not display a psychiatric or neurodevelopmental phenotype, and not all those affected will possess the risk variant. However, the findings highlight commonalities across different neurodevelopmental disorders and the prospect of expanding neurobiological understanding of psychiatric disorders.
Summary of the article
J Am Acad Child Adolesc Psychiatry. 2013 Aug;52(8):772-4.
are of small effect sizes.