Copy Number Variants (CNVs) and Their Role in Anorexia Nervosa

Copy number variants (CNVs) are changes in DNA where sections are either repeated (duplication) or absent (deletion). These genetic differences can affect how genes work, with larger CNVs potentially causing bigger effects. Rare CNVs might be more important for rarer disorders-like anorexia nervosa-than common CNVs.

Anorexia nervosa is a complex psychiatric disorder. Earlier research showed that genetics can play an important role in anorexia nervosa. Links between CNVs and other psychiatric traits like schizophrenia and neurodevelopmental disorders like autism spectrum disorders (ASD) had already been found. Yet the role of CNVs in anorexia nervosa had not been studied in depth until now.

How This Study Was Carried Out
The Anorexia Nervosa Genetics Initiative (ANGI) analysed the DNA of over 7,000 individuals with anorexia nervosa and more than 5,000 without it (control group). This study then focused on identifying and comparing rare CNVs-found in less than 1% of the population-between the two groups.

Key Findings
This study did not find greater numbers of rare CNVs in anorexia nervosa participants compared to control participants. The researchers found no link between anorexia nervosa and the known CNVs associated with other psychiatric traits. However, they made the new discovery of 21 rare CNVs that were not previously known to have psychiatric impacts, but seem to increase the risk of anorexia nervosa. These CNVs were mapped to places on the genome where there are genes involved in metabolism, brain cell signalling, and cellular energy production, which could help explain some biological aspects of the disorder.

What These Findings Mean for Anorexia Nervosa
The newly-discovered CNVs highlight genes with roles in brain function or metabolism, supporting the recent understanding that anorexia nervosa involves both psychiatric and metabolic factors. Some of the highlighted genes were previously linked to other psychiatric traits, suggesting these genes are likely important for multiple psychiatric traits.

Before this study, it was not known how important rare CNVs would be for the risk of developing anorexia nervosa. Would rare CNVs be heavily involved, like for schizophrenia? Or would rare CNVs add only a small amount of risk, like for bipolar disorder? These findings now suggest that the role of CNVs in anorexia is smaller, like bipolar disorder.

Summary 

Biologically meaningful rare CNVs were shown to be involved in anorexia nervosa. However, the role of CNVs in anorexia nervosa is different than the role of CNVs in some other psychiatric traits like schizophrenia. It is likely that CNVs have a small role compared to other genetic factors involved in anorexia nervosa. Importantly, genetic factors are just one piece of the puzzle, with environmental factors also playing a key role in anorexia nervosa.

Further research is needed to enable more detailed understanding of how genetics affect the risk of developing anorexia nervosa. Improved understanding of genetic risk factors could pave the way for identifying people at high-risk or early stages of anorexia nervosa, and ultimately aim for early interventions for those at risk of developing anorexia nervosa.

Link to scientific paper about this study: Genome-wide copy number variation association study in anorexia nervosa | Molecular Psychiatry (nature.com)