Mr William Reay

Mr William Reay

Research student

Career Summary

Biography

William is a PhD candidate under the supervision of Professor Murray Cairns and Professor Melissa Green (UNSW). His research focuses on integrating statistical genetics with systems biology to further our understanding of the biological processes involved in complex disorders and how this could be leveraged for treatment. He is particularly passionate about the application of this approach to psychiatry, as novel interventions remain urgently required to improve patient outcomes.  His research has thus far been published in prestigious journals including Molecular Psychiatry and Brain, Behavior, and Immunity and presented at conferences including the World Congress of Psychiatric Genetics and Schizophrenia International Research Society. He has also participated as a contributing analyst in two large genome-wide association study consortia (ENIGMA and CHARGE).

William is proficient in a wide-range of research skills related to statistical and bioinformatic analyses, including:

  • Genome-wide association studies (GWAS)
  • Multi-marker tests of genetic association
  • Functional integration of molecular quantitative trait loci
  • Rare variant association studies (RVAS)
  • Next-generation sequencing analysis pipelines, including large scale whole-exome (WES) and whole-genome (WGS) datasets
  • Mendelian Randomisation
  • Polygenic risk scoring
  • Analysis of gene-expression data



Keywords

  • Bioinformatics
  • Functional Genomics
  • Genomics
  • Precision Medicine
  • Statistical Genetics
  • Systems Biology

Languages

  • English (Mother)
  • German (Working)

Fields of Research

Code Description Percentage
060102 Bioinformatics 50
060408 Genomics 40
010402 Biostatistics 10

Professional Experience

Academic appointment

Dates Title Organisation / Department
4/4/2018 -  PhD Candidate - Medical Genetics School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle
Australia

Awards

Award

Year Award
2018 Dunkley Medal for Excellence in Biomedical Research
School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle
2018 Faculty of Health and Medicine Medal
Faculty of Health and Medicine, The University of Newcastle
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (12 outputs)

Year Citation Altmetrics Link
2020 Reay WR, Cairns MJ, 'The role of the retinoids in schizophrenia: genomic and clinical perspectives', Molecular Psychiatry, 25 706-718 (2020)

© 2019, The Author(s). Signalling by retinoid compounds is vital for embryonic development, with particular importance for neurogenesis in the human brain. Retinoids, metabolites ... [more]

© 2019, The Author(s). Signalling by retinoid compounds is vital for embryonic development, with particular importance for neurogenesis in the human brain. Retinoids, metabolites of vitamin A, exert influence over the expression of thousands of transcripts genome wide, and thus, act as master regulators of many important biological processes. A significant body of evidence in the literature now supports dysregulation of the retinoid system as being involved in the aetiology of schizophrenia. This includes mechanistic insights from large-scale genomic, transcriptomic and, proteomic studies, which implicate disruption of disparate aspects of retinoid biology such as transport, metabolism, and signalling. As a result, retinoids may present a valuable clinical opportunity in schizophrenia via novel pharmacotherapies and dietary intervention. Further work, however, is required to expand on the largely observational data collected thus far and confirm causality. This review will highlight the fundamentals of retinoid biology and examine the evidence for retinoid dysregulation in schizophrenia.

DOI 10.1038/s41380-019-0566-2
Citations Scopus - 4Web of Science - 3
Co-authors Murray Cairns
2020 Reay WR, Cairns MJ, 'Pairwise common variant meta-analyses of schizophrenia with other psychiatric disorders reveals shared and distinct gene and gene-set associations', TRANSLATIONAL PSYCHIATRY, 10 (2020) [C1]
DOI 10.1038/s41398-020-0817-7
Co-authors Murray Cairns
2020 Reay WR, Atkins JR, Carr VJ, Green MJ, Cairns MJ, 'Pharmacological enrichment of polygenic risk for precision medicine in complex disorders', Scientific Reports, 10 (2020)

© 2020, The Author(s). Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS ha... [more]

© 2020, The Author(s). Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to be directly informative for clinical interventions. We therefore sought to develop a framework to quantify an individual¿s common variant enrichment in clinically actionable systems responsive to existing drugs. This was achieved with a metric designated the pharmagenic enrichment score (PES), which we demonstrate for individual SNP profiles in a cohort of cases with schizophrenia. A large proportion of these had elevated PES in one or more of eight clinically actionable gene-sets enriched with schizophrenia associated common variation. Notable candidates targeting these pathways included vitamins, antioxidants, insulin modulating agents, and cholinergic drugs. Interestingly, elevated PES was also observed in individuals with otherwise low common variant burden. The biological saliency of PES profiles were observed directly through their impact on gene expression in a subset of the cohort with matched transcriptomic data, supporting our assertion that this gene-set orientated approach could integrate an individual¿s common variant risk to inform personalised interventions, including drug repositioning, for complex disorders such as schizophrenia.

DOI 10.1038/s41598-020-57795-0
Co-authors Murray Cairns
2020 Grasby KL, Jahanshad N, Painter JN, Colodro-Conde L, Bralten J, Hibar DP, et al., 'The genetic architecture of the human cerebral cortex.', Science, 367 (2020)
DOI 10.1126/science.aay6690
Citations Scopus - 30Web of Science - 9
Co-authors Murray Cairns, Pat Michie, Rodney Scott, Frans Henskens, Ulrich Schall, Carmel Loughland, Paul Tooney
2020 Adams DM, Reay WR, Geaghan MP, Cairns MJ, 'Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa', Neuropsychopharmacology, (2020)

© 2020, The Author(s). Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an... [more]

© 2020, The Author(s). Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an attractive target for clinical intervention as glycaemia can be modulated by both lifestyle factors and pharmacological agents. However, observational studies are inherently confounded, and therefore, causal relationships cannot be reliably established. We employed genetic variants rigorously associated with three glycaemic traits (fasting glucose, fasting insulin, and glycated haemoglobin) as instrumental variables in a two-sample Mendelian randomisation analysis to investigate the causal effect of these measures on the risk for eight psychiatric disorders. A significant protective effect of a natural log transformed pmol/L increase in fasting insulin levels was observed for anorexia nervosa after the application of multiple testing correction (OR = 0.48 [95% CI: 0.33-0.71]¿inverse-variance weighted estimate). There was no consistently strong evidence for a causal effect of glycaemic factors on the other seven psychiatric disorders considered. The relationship between fasting insulin and anorexia nervosa was supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between insulin levels and anorexia.[Figure not available: see fulltext.][Figure not available: see fulltext.]

DOI 10.1038/s41386-020-00847-w
Co-authors Murray Cairns
2020 Adams D, Reay W, Geaghan M, Cairns M, 'Investigating the effect of glycaemic traits on the risk of psychiatric illness using Mendelian randomisation (2020)
DOI 10.1101/2020.03.09.984690
Co-authors Murray Cairns
2020 Reay W, Shair SE, Geaghan M, Riveros C, Holiday E, McEvoy M, et al., 'Genetically informed precision drug repurposing for lung function and implications for respiratory infection (2020)
DOI 10.1101/2020.06.25.20139816
Co-authors John Attia, Roseanne Peel, Rodney Scott
2020 Reay WR, Atkins JR, Quidé Y, Carr VJ, Green MJ, Cairns MJ, 'Polygenic disruption of retinoid signalling in schizophrenia and a severe cognitive deficit subtype', Molecular Psychiatry, 25 719-731 (2020) [C1]

© 2018, The Author(s). Retinoid metabolites of vitamin A are intrinsically linked to neural development, connectivity and plasticity, and have been implicated in the pathophysiolo... [more]

© 2018, The Author(s). Retinoid metabolites of vitamin A are intrinsically linked to neural development, connectivity and plasticity, and have been implicated in the pathophysiology of schizophrenia. We hypothesised that a greater burden of common and rare genomic variation in genes involved with retinoid biogenesis and signalling could be associated with schizophrenia and its cognitive symptoms. Common variants associated with schizophrenia in the largest genome-wide association study were aggregated in retinoid genes and used to formulate a polygenic risk score (PRSRet) for each participant in the Australian Schizophrenia Research Bank. In support of our hypothesis, we found PRSRet to be significantly associated with the disorder. Cases with severe cognitive deficits, while not further differentiated by PRSRet, were enriched with rare variation in the retinoic acid receptor beta gene RARB, detected through whole-genome sequencing. RARB rare variant burden was also associated with reduced cerebellar volume in the cases with marked cognitive deficit, and with covariation in grey matter throughout the brain. An excess of rare variation was further observed in schizophrenia in retinoic acid response elements proximal to target genes, which we show are differentially expressed in the disorder in two RNA sequencing datasets. Our results suggest that genomic variation may disrupt retinoid signalling in schizophrenia, with particular significance for cases with severe cognitive impairment.

DOI 10.1038/s41380-018-0305-0
Citations Scopus - 8Web of Science - 5
Co-authors Murray Cairns
2020 Liu X, Low SK, Atkins JR, Wu JQ, Reay WR, Cairns HM, et al., 'Wnt receptor gene FZD1 was associated with schizophrenia in genome-wide SNP analysis of the Australian Schizophrenia Research Bank cohort', Australian and New Zealand Journal of Psychiatry, 54 902-908 (2020) [C1]

© The Royal Australian and New Zealand College of Psychiatrists 2019. Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to... [more]

© The Royal Australian and New Zealand College of Psychiatrists 2019. Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories. Methods: We performed a case¿control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome. Results: The strongest finding (p = 2.01 × 10-6, odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance (p = 2.78 × 10-6). Conclusion: The identification of FZD1, as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

DOI 10.1177/0004867419885443
Co-authors Murray Cairns, Pat Michie, Rodney Scott, Frans Henskens, Carmel Loughland, Paul Tooney, Ulrich Schall
2019 Reay W, Atkins J, Carr V, Green M, Cairns M, 'Pharmacological enrichment of polygenic risk for precision medicine in complex disorders (2019)
DOI 10.1101/655001
Co-authors Murray Cairns
2019 Nakamura JP, Schroeder A, Hudson M, Jones N, Gillespie B, Du X, et al., 'The maternal immune activation model uncovers a role for the Arx gene in GABAergic dysfunction in schizophrenia', Brain, Behavior, and Immunity, 81 161-171 (2019) [C1]

© 2019 Elsevier Inc. A hallmark feature of schizophrenia is altered high frequency neural oscillations, including reduced auditory-evoked gamma oscillatory power, which is underpi... [more]

© 2019 Elsevier Inc. A hallmark feature of schizophrenia is altered high frequency neural oscillations, including reduced auditory-evoked gamma oscillatory power, which is underpinned by parvalbumin (PV) interneuron dysfunction. Maternal immune activation (MIA) in rodents models an environmental risk factor for schizophrenia and recapitulates these PV interneuron changes. This study sought to link reduced PV expression in the MIA model with alterations to auditory-evoked gamma oscillations and transcript expression. We further aligned transcriptional findings from the animal model with human genome sequencing data. We show that MIA, induced by the viral mimetic, poly-I:C in C57Bl/6 mice, caused in adult offspring reduced auditory-evoked gamma and theta oscillatory power paralleled by reduced PV protein levels. We then showed the Arx gene, critical to healthy neurodevelopment of PV interneurons, is reduced in the forebrain of MIA exposed mice. Finally, in a whole-genome sequenced patient cohort, we identified a novel missense mutation of ARX in a patient with schizophrenia and in the Psychiatric Genomics Consortium 2 cohort, a nominal association of proximal ARX SNPs with the disorder. This suggests MIA, as a risk factor for schizophrenia, may be influencing Arx expression to induce the GABAergic dysfunction seen in schizophrenia and that the ARX gene may play a role in the prenatal origins of schizophrenia pathophysiology.

DOI 10.1016/j.bbi.2019.06.009
Citations Scopus - 2Web of Science - 1
Co-authors Murray Cairns
2019 Reay W, Cairns M, 'Pairwise common variant meta-analyses of schizophrenia with other psychiatric disorders reveals shared and distinct gene and gene-set associations (2019)
DOI 10.1101/725614
Co-authors Murray Cairns
Show 9 more journal articles

Conference (1 outputs)

Year Citation Altmetrics Link
2018 Reay W, Atkins J, Fitzsimmons C, Green M, Carr V, Cairns M, 'DYSREGULATION OF RETINOID SIGNALLING IN SCHIZOPHRENIA OBSERVED IN WHOLE GENOME SEQUENCE ANALYSIS', SCHIZOPHRENIA BULLETIN, Florence, ITALY (2018)
Co-authors Murray Cairns
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Grants and Funding

Summary

Number of grants 4
Total funding $7,200

Click on a grant title below to expand the full details for that specific grant.


20192 grants / $3,700

2019 Young Investigator Travel Award$2,200

Funds awarded to present a research poster-talk at the 7th Annual Molecular Psychiatry Meeting in San Francisco, California. 

Funding body: 7th Annual Molecular Psychiatry Meeting

Funding body 7th Annual Molecular Psychiatry Meeting
Scheme Young Investigator Travel Award
Role Lead
Funding Start 2019
Funding Finish 2019
GNo
Type Of Funding External
Category EXTE
UON N

Centre for Brain and Mental Health Research 2019 Travel Grant Round$1,500

Grant to assist travel to present research at the 2019 World Congress of Psychiatric Genetics, Anaheim, California

Funding body: Centre for Brain and Mental Health Research

Funding body Centre for Brain and Mental Health Research
Scheme CBMHR Travel Grant Round
Role Lead
Funding Start 2019
Funding Finish 2019
GNo
Type Of Funding C1700 - Aust Competitive - Other
Category 1700
UON N

20182 grants / $3,500

Centre for Brain and Mental Health Research Summer Research Internship $2,000

Funds to complete a summer research internship to gain experience in the analysis of whole-genome sequencing data

Funding body: Centre for Brain and Mental Health Research

Funding body Centre for Brain and Mental Health Research
Scheme Summer Research Internship
Role Lead
Funding Start 2018
Funding Finish 2018
GNo
Type Of Funding C1700 - Aust Competitive - Other
Category 1700
UON N

Centre for Brain and Mental Health Research 2018 Travel Grant Round$1,500

Grant to assist travel to present research at the 2018 World Congress of Psychiatric Genetics, Glasgow, Scotland. 

Funding body: Centre for Brain and Mental Health Research

Funding body Centre for Brain and Mental Health Research
Scheme CBMHR Travel Grant Round
Role Lead
Funding Start 2018
Funding Finish 2018
GNo
Type Of Funding C1700 - Aust Competitive - Other
Category 1700
UON N
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Mr William Reay

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