New genetic links uncovered in study of almost 700,000 people living with anxiety

  • A new study of almost 700,000 people, which was co-authored by a Queen’s University researcher, has found the largest number of genetic links with anxiety to date.

    Anxiety disorders are the most prevalent mental health conditions worldwide. Around eight million people in the UK are currently estimated to be living with anxiety (Mental Health UK). Symptoms vary in intensity and can range from healthy stress responses to a debilitating disorder.

    Professor Cherie Armour from the School of Psychology at Queen’s is a co-author of a new research study, which was led by King’s College London and QIMR Berghofer medical research institute. It has been published in a world leading journal, Nature Human Behaviour.

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    The research, which is a genome wide association study (GWAS), analysed genetic data on anxiety symptoms in almost 700,000 people of European ancestry. This offers new insight into the genetic pathways of the condition.

    By exploring DNA, the researchers were able to pinpoint which genetic differences occur more often in those who experience more severe anxiety symptoms.

    The study revealed that:

    • There were 74 locations where genetic differences were linked to anxiety symptoms. Half of these were previously reported in studies but 39 were novel findings.
    • Many genes such as PCLO and SORCS3 are particularly active in brain tissue and play a role in how nerve cells communicate with each other.
    • Common genetic variation explains around six per cent of the differences in anxiety symptom severity between people.

    This highlights that environmental influences, gene-environment interactions, and undetected genetic effects could all be factors.

    Professor Cherie Armour from the School of Psychology at Queen's University Belfast, a co-author on the study, explains: "Anxiety is one of the most common mental health conditions in our society and this study is an important step forward. It underlines that biological risk works hand in hand with people's experiences and environments. Understanding both is how we'll improve prevention and support.

    “Research on this scale is only possible through international collaboration, bringing together hundreds of thousands of people as research participants and using expertise from across the world. I hope that findings like these help us identify who may be most vulnerable, so that we can reach people earlier and offer the right support before symptoms become debilitating.”

    Professor Thalia Eley is Professor of Developmental Behavioural Genetics at Institute of Psychiatry, Psychology and Neuroscience (IoPPN) King’s College London and lead author on the study. She says: “Despite the public health impact of anxiety, progress in the understanding of its genetics lags behind other major mental health conditions. Given the high and rising rates of anxiety, especially in young adults, it is more important than ever to improve our ability to identify and understand sources of risk.

    “We hope our findings encourage a new wave of large-scale analyses to accelerate our progress in understanding the genetic architecture of anxiety.”

    Dr Megan Skelton, Research Fellow at IoPPN, King’s College London and first author on the study, comments: “This is an exciting step forward in understanding how anxiety risk can be influenced by biological processes. It's important to highlight that even someone with a very high genetic risk might not develop anxiety, and someone with a low genetic risk could.

    “Genetic influences work alongside and interplay with life experiences, social contexts, and psychological factors to shape individual risk. The rise we're seeing in anxiety rates points to environmental factors, and understanding genetic risk can help us to identify who may be most vulnerable to those factors, ultimately contributing to more effective prevention and treatment strategies.”

    The study also calculated polygenic scores for anxiety – this is a summary of an individual’s genetic risk. The scores were created using the European-ancestry GWAS results, in separate samples of people from European, African and South Asian populations, and explained 1.2 per cent to 2.9 per cent of the variance in anxiety symptom severity.

    The scores suggest there may be some shared genetic variants across the groups, but more data is necessary to identify population-specific genetic risk. Currently, there is not enough data on both anxiety symptoms and genetics in people with African or South Asian ancestry.

    The researchers also found that there was a broad range of significant genetic correlations of anxiety with both mental and physical health conditions, including depression, irritable bowel syndrome, chronic pain, coronary artery disease, endometriosis and migraine.

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    Dr Brittany Mitchell is Team Head of The Complex Trait Genomics group at the QIMR Berghofer Medical Research Institute and co-first author on the study. She explains: “These correlations highlight the interconnection between mental and physical health. Importantly, while some shared genetic variants may increase risk for both a physical health condition and more severe anxiety symptoms, it’s also true that living with chronic pain or illness can contribute to anxiety symptoms. Our findings don’t reveal causation or the direction of effect, but they do open up important questions for future research.”

    The study was an output of the Psychiatric Genomics Consortium, which is a group of scientists that focus on meta and mega-analyses of psychiatric genetic studies.

    This work was partially funded by the US National Institute for Health (NIH) and researchers were supported by a range of bodies including the Wellcome Trust, the Medical Research Council (MRC), the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the Australian National Health and Medical Research Council.

     

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