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Rare genetic changes associated with increased risk of depression

24 April 2019

Kim Kendall
Dr Kimberely Kendall

Researchers at Cardiff University have identified an association between rare changes in our genetic code, called copy number variants (CNVs), and the risk of developing depression.

Rare CNVs have previously been shown to increase an individual’s risk of experiencing a range of neurodevelopmental disorders including schizophrenia, intellectual disability, attention deficit hyperactivity disorder (ADHD) and autism. However, the impact of these variants on the risk for depression has previously been unclear.

Using data from the UK Biobank, the research team examined the role of 53 CNVs known to be associated with increased risk of neurodevelopmental disorders in risk of depression in over 400,000 individuals with European genetic ancestry.

“We found that as a group, neurodevelopmental CNVs increased the risk of depression by between 1.34 and 1.51 times, depending on how depression was defined. We used three definitions; self-reported depression, self-reported depression with current anti-depressant prescription and hospital discharge diagnosis,” said Dr Kimberley Kendall, Wellcome Trust Clinical Research Fellow at the university’s MRC Centre for Neuropsychiatric Genetics and Genomics.

Dr Kendall and her colleagues conducted further analyses to investigate whether this association could be explained by variables linked to increased risk of depression, including physical health, educational attainment, social deprivation, smoking status and alcohol consumption.

While each of these variables could partially explain the association, in total they only accounted for a very small proportion of the relationship. A strong independent association between neurodevelopmental CNVs and depression remained in our analyses when incorporating these measures.

Dr Kimberley Kendall Wellcome Trust Clinical Research Fellow, Division of Psychological Medicine and Clinical Neurosciences

Professor James Walters, corresponding author on the paper said, “This is an important addition to what we know about these genetic risk factors, reiterating that carriers of CNVs without neurodevelopmental disorders cannot be assumed to be unimpaired.”

The paper, Association of Rare Copy Number Variants with Risk of Depression,is published in JAMA Psychiatry.

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