Publications
Please find summaries of written reports of studies our researchers have contributed to. To view the entire scientific paper, please follow the links provided or email us for a copy of the research article of interest.
New Publication Alert!
We are delighted to share our latest publication, “Shared Genetic Links Between Sleep, Neurodevelopmental and Neuropsychiatric Conditions: A Genome-Wide and Pathway-Based Polygenic Score Analysis”, which has been published in Genes, Brain and Behavior. This work is a significant contribution to our understanding of the genetic interplay between sleep disturbances and neurodevelopmental and neuropsychiatric conditions. A special mention goes to lead author Dr Laura Fahey, who was a postdoctoral researcher on our team during this project.
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Key Findings:
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Polygenic scores for autism, bipolar disorder, schizophrenia and major depression were associated with an evening chronotype.
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Polygenic scores for ADHD, autism, bipolar disorder, schizophrenia, and major depression were associated with insomnia.
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Biological Pathways: While shared genetic variation between most phenotype pairs was not enriched in specific biological pathways—likely due to the highly polygenic nature of these traits or potential tissue-specific effects—we made a notable discovery. Shared genetic variation between bipolar disorder and chronotype was enriched in two pathways:
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KEAP1–NRF2 Pathway: Known for its role in oxidative stress response and regulation by the circadian clock.
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mRNA Splicing—Minor Pathway: Previously shown to be partially influenced by circadian rhythms.
These findings provide further support for the hypothesis that disrupted circadian rhythms play a critical role in the pathology of bipolar disorder.
Acknowledgements: This research was made possible by funding from the European Research Council (ERC) Starting Investigator Grant, awarded to Professor Lorna Lopez under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 950010).
Polygenic scores stratify neurodevelopmental copy number variant carrier cognitive outcomes in the UK Biobank
Deletions or duplications of DNA segments are found throughout most people's genomes and are referred to as copy-number variants (CNVs). Yet, some rare versions of these CNVs have been linked to neuropsychiatric conditions including autism, intellectual disability and schizophrenia. These CNVs are known as ND-CNVs. Interestingly, despite strong associations to neuropsychiatric conditions, some individuals with ND-CNVs present with no clinically relevant outcomes. Differences in this clinical manifestation are often observed not only between genders but also members of the same family. This makes interpretation of ND-CNVs effects difficult for clinicians and genetic counsellors. However, previous research suggests that additional genetic variation in other regions of the genome can change ND-CNVs outcomes. Leveraging data from the UK Biobank, the world’s largest population-based, biobank databases, this recent study found that a higher presence of common genetic variants, linked to cognition and educational attainment, was associated with improved verbal-numeric scores in ND-CNV carriers. Common genetic variants (population frequency >1%) were measured using polygenic scores which is a method of summarising the summed effects of many genetic variants. However, no such association was found for rare genetic variants. It was also shown that ND-CNV carriers in the lowest decile for cognition and educational attainment polygenic scores were 2-5 times more likely to have low verbal-numeric scores compared to the baseline rate. Results indicate that additional genetic variation could potentially be used to stratify ND-CNV carriers based on their predisposition to psychiatric outcomes and cognitive ability and thus contribute to more personalized approaches in genetic diagnostics and patient care.
Circadian Variation in the Response to Vaccination: A Systematic Review and Evidence Appraisal
The human body has internal timers known as circadian clocks that regulate our daily rhythms, including how our immune system functions. Because of this, the time of day that we receive a vaccination could affect how well our immune system responds. This systematic review investigated whether the time of day of vaccination (TODV) is associated with our immune and clinical responses. 3,114 studies were identified from multiple databases to include TODV and immune responses, with 23 of these meeting our inclusion criteria, making them most relevant for this review. Many of these studies were conducted during the COVID-19 pandemic when vaccinations were widespread.
Although these studies were of a similar nature, there were many differences in their approaches. They varied in things like who was involved, which vaccines were used, and whether factors like sleep patterns or work shifts were considered. Despite these differences, some studies suggested that getting vaccinated in the afternoon might lead to a better immune response, while others said morning was best, or that it didn't really matter.
Overall, we need more research to understand if the time of day we get vaccinated affects how well our immune system responds, and if any potential benefits outweigh any downsides, like making it harder for people to attend vaccination appointments and reducing the numbers that can be vaccinated in a day.
Neuropsychiatric disorders, chronotype and sleep: A narrative review of GWAS findings and the application of Mendelian randomization to investigate causal relationships
Genome-wide association studies (GWAS) have helped us to find the specific variants that are related to sleep phenotypes and neuropsychiatric phenotypes. Chronotype is a person’s natural tendency towards being a morning person or a night owl. GWAS has identified a significant genetic component for chronotype. We have used Mendelian Randomisation (MR), a statistical model that can use genetic information to study if there is a cause-and-effect relationship between chronotype and neuropsychiatric phenotypes. This review discusses the main findings from GWAS for neuropsychiatric phenotypes and chronotype and how MR has been used to understand the link between them. The evidence suggests that there is a two-way relationship between sleep and neuropsychiatric phenotypes and gives clues about what factors may be useful for further investigation.
Establishing an Irish autism research network
In September, we published a letter to the editor of the Irish Journal of Psychological Medicine. This letter shares our experience organising and hosting a Thesis In Three event as we discuss in our interview here in our blog, 'Autism Research Thesis In Three'. In this article we have collected resources that we find useful when approaching engagement and public patient involvement (PPI) in our research. Take a look at the published letter and the supplemental materials to find out more.
Susceptibility to the common cold virus is associated with day length
Seasonal rhythms are endogenous timing mechanisms that allow animals living at temperate latitudes to synchronize their physiology to the seasons. Human viral respiratory disease is prevalent in the winter at temperate latitudes, but the role of endogenous mechanisms in these recurring annual patterns is unclear. The Common Cold Project is a repository of data describing the experimental viral challenge of 1,337 participants across the seasons of the year. We report a secondary analysis of these data to investigate if susceptibility to the common cold is associated with day length. The majority of the participants (78%) showed signs of infection but only 32% developed clinical signs of disease, and the probability of infection was significantly higher in longer day lengths (summer), but the disease was more likely in short (winter) day lengths. The persistence of winter disease patterns in experimental conditions supports the role of endogenous seasonality in human susceptibility to viral infection.
Brief Report: Evaluating the Diagnostic Yield of Commercial Gene Panels in Autism
Effective clinical diagnostics for neurodevelopmental conditions could have beneficial psychiatric and medical implications for autistic individual’s and their families. Candidate genetic variations suggested to increase one’s likelihood of autism does not apply to all autism cases. This results in the prospect of efficient diagnostics for autism being limited due to the extensive degree of both genotypic and phenotypic heterogeneity. Ní Ghrálaigh et al evaluate how marketed applications for autism diagnostics are limited due to the lack of standardized curation of gene-condition relationships in findings from research groups. To read more about their conclusions about the clinical utility of these gene panels, please read this research article.
How does genetic variation modify ND-CNV phenotypes?
This opinion article explores the current outstanding questions surrounding the clinical genomics of variants called copy number variants (CNVs) in those that carrier genetic variants that are related to neurodevelopment. Dinneen et al., discuss how common and rare types of risk variants may contribute to the varied traits and clinical outcomes associated with neurodevelopmental conditions. For more about integrated genetic variant approaches, the clinical interpretation of genetic variants and challenges in relation to future clinical translation, please follow the link below to read this recently published article.
Autism spectrum disorder genomics: The progress and potential of genomic technologies
As researchers are now capable of recording genomic information in the form of data, there is evidence that there is a genetic basis for neurodevelopmental conditions such as autism. This scientific paper discusses the genetic basis of autism, the progress of autism studies using genomic technologies and why these technologies are important for clinical and healthcare research.
Please contact us if you would like access to the entire paper.