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2. Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest

Author

Eastwood, Glenn, primary, Nichol, Alistair D., additional, Hodgson, Carol, additional, Parke, Rachael L., additional, McGuinness, Shay, additional, Nielsen, Niklas, additional, Bernard, Stephen, additional, Skrifvars, Markus B., additional, Stub, Dion, additional, Taccone, Fabio S., additional, Archer, John, additional, Kutsogiannis, Demetrios, additional, Dankiewicz, Josef, additional, Lilja, Gisela, additional, Cronberg, Tobias, additional, Kirkegaard, Hans, additional, Capellier, Gilles, additional, Landoni, Giovanni, additional, Horn, Janneke, additional, Olasveengen, Theresa, additional, Arabi, Yaseen, additional, Chia, Yew Woon, additional, Markota, Andrej, additional, Hænggi, Matthias, additional, Wise, Matt P., additional, Grejs, Anders M., additional, Christensen, Steffen, additional, Munk-Andersen, Heidi, additional, Granfeldt, Asger, additional, Andersen, Geir Ø., additional, Qvigstad, Eirik, additional, Flaa, Arnljot, additional, Thomas, Matthew, additional, Sweet, Katie, additional, Bewley, Jeremy, additional, Bäcklund, Minna, additional, Tiainen, Marjaana, additional, Iten, Manuela, additional, Levis, Anja, additional, Peck, Leah, additional, Walsham, James, additional, Deane, Adam, additional, Ghosh, Angajendra, additional, Annoni, Filippo, additional, Chen, Yan, additional, Knight, David, additional, Lesona, Eden, additional, Tlayjeh, Haytham, additional, Svenšek, Franc, additional, McGuigan, Peter J., additional, Cole, Jade, additional, Pogson, David, additional, Hilty, Matthias P., additional, Düring, Joachim P., additional, Bailey, Michael J., additional, Paul, Eldho, additional, Ady, Bridget, additional, Ainscough, Kate, additional, Hunt, Anna, additional, Monahan, Sinéad, additional, Trapani, Tony, additional, Fahey, Ciara, additional, and Bellomo, Rinaldo, additional

Published
2023
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5. DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli

Author

Frodl, Thomas, Szyf, Moshe, Carballedo, Angela, Ly, Victoria, Dymov, Sergiy, Vaisheva, Farida, Morris, Derek, Fahey, Ciara, Meaney, James, Gill, Michael, and Booij, Linda

Subjects
Methylation, Depression, Mental, Serotonin, Health, Psychology and mental health
Abstract

Background: The aim of the present study was to investigate the association of fMRI blood oxygen-level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). Methods: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing. Results: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. Limitations: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. Conclusion: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery., Introduction Childhood adversity, such as childhood maltreatment, plays an important role in a number of multifactorial mental disorders. Recent studies reveal that certain aspects of stress-related mental disorders result from [...]

Published
2015
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8. Signatures of mutation and selection in the cancer genome

Author

Bignell, Graham R., Greenman, Chris D., Davies, Helen, Butler, Adam P., Edkins, Sarah, Andrews, Jenny M., Buck, Gemma, Chen, Lina, Beare, David, Latimer, Calli, Widaa, Sara, Hinton, Jonathon, Fahey, Ciara, Fu, Beiyuan, Swamy, Sajani, Dalgliesh, Gillian L., Teh, Bin T., Deloukas, Panos, Yang, Fengtang, Campbell, Peter J., Futreal, P. Andrew, and Stratton, Michael R.

Subjects
Gene mutations -- Health aspects -- Research, Carcinogenesis -- Risk factors -- Genetic aspects -- Research, Cancer -- Genetic aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery., The genome of a cancer cell usually carries several somatic changes (1). A subset, termed 'driver' mutations, confer clonal growth advantage, are positively selected and are causally implicated in cancer [...]

Published
2010
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10. An inherited duplication at the gene p21 Protein-Activated Kinase 7 (PAK7) is a risk factor for psychosis

Author

Morris, Derek W., Pearson, Richard D., Cormican, Paul, Kenny, Elaine M., OʼDushlaine, Colm T., Perreault, Louis-Philippe Lemieux, Giannoulatou, Eleni, Tropea, Daniela, Maher, Brion S., Wormley, Brandon, Kelleher, Eric, Fahey, Ciara, Molinos, Ines, Bellini, Stefania, Pirinen, Matti, Strange, Amy, Freeman, Colin, Thiselton, Dawn L., Elves, Rachel L., Regan, Regina, Ennis, Sean, Dinan, Timothy G., McDonald, Colm, Murphy, Kieran C., OʼCallaghan, Eadbhard, Waddington, John L., Walsh, Dermot, OʼDonovan, Michael, Grozeva, Detelina, Craddock, Nick, Stone, Jennifer, Scolnick, Ed, Purcell, Shaun, Sklar, Pamela, Coe, Bradley, Eichler, Evan E., Ophoff, Roel, Buizer, Jacobine, Szatkiewicz, Jin, Hultman, Christina, Sullivan, Patrick, Gurling, Hugh, Mcquillin, Andrew, St Clair, David, Rees, Elliott, Kirov, George, Walters, James, Blackwood, Douglas, Johnstone, Mandy, Donohoe, Gary, OʼNeill, Francis A., Kendler, Kenneth S., Gill, Michael, Riley, Brien P., Spencer, Chris C. A., and Corvin, Aiden

Published
2014
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17. Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP). A Phase II, Multicenter Randomized Controlled Clinical Trial

Author

Hodgson, Carol L., primary, Cooper, D. James, additional, Arabi, Yaseen, additional, King, Victoria, additional, Bersten, Andrew, additional, Bihari, Shailesh, additional, Brickell, Kathy, additional, Davies, Andrew, additional, Fahey, Ciara, additional, Fraser, John, additional, McGuinness, Shay, additional, Murray, Lynne, additional, Parke, Rachael, additional, Paul, Eldho, additional, Tuxen, David, additional, Vallance, Shirley, additional, Young, Meredith, additional, and Nichol, Alistair, additional

Published
2019
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19. Magnetic resonance imaging in comatose adults resuscitated after out-of-hospital cardiac arrest: A posthoc study of the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest trial

Author

Eastwood, Glenn M., Bailey, Michael, Nichol, Alistair D., Dankiewicz, Josef, Nielsen, Niklas, Parke, Rachael, Cronberg, Tobias, Olasveengen, Theresa, Grejs, Anders M., Iten, Manuela, Haenggi, Matthias, McGuigan, Peter, Wagner, Franca, Moseby-Knappe, Marion, Lang, Margareta, Bellomo, Rinaldo, Hodgson, Carol, McGuinness, Shay, Bernard, Stephen, Skrifvars, Markus B., Stub, Dion, Taccone, Fabio S., Archer, John, Kutsogiannis, Demetrios, Lilja, Gisela, Kirkegaard, Hans, Capellier, Gilles, Landoni, Giovanni, Horn, Janneke, Arabi, Yaseen, Chia, Yew Woon, Markota, Andrej, Wise, Matt P., Christensen, Steffen, Munk-Andersen, Heidi, Granfeldt, Asger, Andersen, Geir Ø., Qvigstad, Eirik, Flaa, Arnljot, Thomas, Matthew, Sweet, Katie, Bewley, Jeremy, Bäcklund, Minna, Tiainen, Marjaana, Levis, Anja, Peck, Leah, Walsham, James, Deane, Adam, Ghosh, Angajendra, Annoni, Filippo, Chen, Yan, Knight, David, Lesona, Eden, Tlayjeh, Haytham, Svenšek, Franc, Cole, Jade, Pogson, David, Hilty, Matthias P., Düring, Joachim P., Paul, Eldho, Ady, Bridget, Ainscough, Kate, Hunt, Anna, Monahan, Sinéad, Trapani, Tony, and Fahey, Ciara

Abstract

Neuroimaging with magnetic resonance imaging (MRI) may assist clinicians in evaluating brain injury and optimising care in comatose adults resuscitated after out-of-hospital cardiac arrest (OHCA). However, contemporary international data on its use are lacking.

Published
2024
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20. Association between single nucleotide polymorphism of the FKBP5 gene and neural correlates of attentional bias towards emotional stimuli in depression

Author

Meaney James, Morris Derek, Wetterling Friedrich, Carballedo Angela, O'Keane Veronica, McCarthy Hazel, Fahey Ciara, Gill Michael, Tozzi Leonardo, and Frodl Thomas

Subjects
Neural correlates of consciousness, General Neuroscience, Emotional stimuli, Single-nucleotide polymorphism, Attentional bias, Association (psychology), Psychology, Neuroscience, Depression (differential diagnoses), FKBP5 Gene, Developmental psychology
Published
2014
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21. Genetic Basis of Y-Linked Hearing Impairment

Author

Wang, Qiuju, Xue, Yali, Zhang, Yujun, Long, Quan, Yang, Fengtang, Turner, Daniel J., Fitzgerald, Tomas, Ng, Bee Ling, Zhao, Yali, Chen, Yuan, Liu, Qingjie, Yang, Weiyan, Han, Dongyi, Quail, Michael A., Swerdlow, Harold, Burton, John, Fahey, Ciara, Ning, Zemin, Hurles, Matthew E., Carter, Nigel P., Yang, Huanming, and Tyler-Smith, Chris

Published
2013
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23. Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression

Author

Tozzi, Leonardo, primary, Carballedo, Angela, additional, Wetterling, Friedrich, additional, McCarthy, Hazel, additional, O'Keane, Veronica, additional, Gill, Michael, additional, Morris, Derrek, additional, Fahey, Ciara, additional, Meaney, James, additional, and Frodl, Thomas, additional

Published
2015
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24. DNA Methylation of the Serotonin Transporter Gene in Peripheral Cells and Stress-Related Changes in Hippocampal Volume: A Study in Depressed Patients and Healthy Controls

Author

Booij, Linda, primary, Szyf, Moshe, additional, Carballedo, Angela, additional, Frey, Eva-Maria, additional, Morris, Derek, additional, Dymov, Sergiy, additional, Vaisheva, Farida, additional, Ly, Victoria, additional, Fahey, Ciara, additional, Meaney, James, additional, Gill, Michael, additional, and Frodl, Thomas, additional

Published
2015
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27. Analysis of the hexanucleotide repeat expansion and founder haplotype at C9ORF72 in an Irish psychosis case-control sample

Author

Fahey, Ciara, primary, Byrne, Susan, additional, McLaughlin, Russell, additional, Kenna, Kevin, additional, Shatunov, Aleksey, additional, Donohoe, Gary, additional, Gill, Michael, additional, Al-Chalabi, Ammar, additional, Bradley, Daniel G., additional, Hardiman, Orla, additional, Corvin, Aiden P., additional, and Morris, Derek W., additional

Published
2014
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28. Effects of a novel schizophrenia risk variant rs7914558 atCNNM2on brain structure and attributional style

Author

Rose, Emma Jane, primary, Hargreaves, April, additional, Morris, Derek, additional, Fahey, Ciara, additional, Tropea, Daniela, additional, Cummings, Elizabeth, additional, Caltagirone, Carlo, additional, Bossú, Paola, additional, Chiapponi, Chiara, additional, Piras, Fabrizio, additional, Spalletta, Gianfranco, additional, Gill, Michael, additional, Corvin, Aiden, additional, and Donohoe, Gary, additional

Published
2014
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31. Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression

Author

Tozzi, Leonardo, Carballedo, Angela, Wetterling, Friedrich, McCarthy, Hazel, O'Keane, Veronica, Gill, Michael, Morris, Derrek, Fahey, Ciara, Meaney, James, and Frodl, Thomas

Abstract

The gene expressing the FK506 binding protein 51 (FKBP5) is involved in the regulation of glucocorticoid receptor sensitivity. The rs1360780 SNP in this gene (T allele vs C homozygous) has been found to be associated with major depressive disorder (MDD). The aim of our study was to investigate whether this polymorphism might be associated with altered brain structure and function in a cohort of 40 patients with MDD and 43 healthy controls. A functional magnetic resonance imaging (fMRI) emotional attention task was employed. Diffusion tensor imaging (DTI) was also conducted, extracting mean diffusivity (MD) and fractional anisotropy (FA) from brain areas that showed functional differences between patients expressing the two alleles of the rs1360780 SNP. Finally, the effect of the interaction of childhood adversity as measured by the Childhood trauma Questionnaire (CTQ) and rs1360780 allele status was analyzed in relation to DTI measures using a general linear model. All results presented are family-wise error (FWE) corrected. Functional interactions were found between genotype and diagnosis (p<0.01). Patients carrying the high-risk allele, compared with patients not carrying it, showed reduced activity in the rolandic operculum, Heschl gyrus, insula, parahippocampal gyrus, posterior cingulate cortex, inferior frontal gyrus (p<0.05 for all measures); and increased MD and reduced FA measures in many of these regions (p<0.05). An interaction between CTQ scores and allele status was associated with DTI changes in the insula, rolandic operculum, and inferior frontal gyrus. Here, the presence of both the high-risk allele and higher CTQ scores was associated with higher MD and lower FA values (p<0.05). In conclusion, MDD patients expressing the T allele of rs1360780, compared with C homozygous patients, exhibit functional and structural differences in areas involved in emotional perception and inhibition. The interaction between the T allele and childhood maltreatment explained our structural findings in these regions, suggesting that their altered maturation and function might be influenced by early chronic stress in the presence of this genetic trait.

Published
2016
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33. A NOS1 variant implicated in cognitive performance influences evoked neural responses during a high density EEG study of early visual perception.

Author

O'Donoghue, Therese, Morris, Derek W., Fahey, Ciara, Costa, Andreia Da, Foxe, John J., Hoerold, Doreen, Tropea, Daniela, Gill, Michael, Corvin, Aiden, and Donohoe, Gary

Abstract

Background: The nitric oxide synthasase-1 gene ( NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear. Methods: We investigated differences in the P1 visual evoked potential in a high density EEG study of 54 healthy participants. Given both NOS1's association with cognition and recent evidence that cognitive performance and P1 response are correlated, we investigated whether NOS1's effect on P1 response was independent of its effects on cognition using CANTAB's spatial working memory (SWM) task. Results: We found that carriers of the previously identified risk 'G' allele showed significantly lower P1 responses than non-carriers. We also found that while P1 response and SWM performance were correlated, NOS1 continued to explain a significant proportion of variation in P1 response even when its effects on cognition were accounted for. Conclusion: The schizophrenia implicated NOS1 variants rs6490121 influences visual sensory processing as measured by the P1 response, either as part of the gene's pleiotropic effects on multiple aspects of brain function, or because of a primary influence on sensory processing that mediates the effects already seen in higher cognitive processes. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Published
2012
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35. Evaluating liquid biopsies for methylomic profiling of prostate cancer

Author

Silva, Romina, Moran, Bruce, Russell, Niamh M., Fahey, Ciara, Vlajnic, Tatjana, Rustom P. Manecksha, Finn, Stephen P., Brennan, Donal J., Gallagher, William M., and Perry, Antoinette S.

Subjects
3. Good health
Abstract

Background: Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, the accuracy of monitoring the tumor methylome using liquid biopsies remains relatively unknown. Objectives: to investigate how well two types of liquid biopsy (urine and blood) capture the prostate cancer methylome, and may thus serve as a non-invasive surrogate for studying the tumor epigenome. Methods: A cohort of four metastatic treatment naïve prostate cancer (PCa) patients was selected. Matched biopsy cores (tumor and histologically matched-normal), post-DRE, pre-biopsy urine, and peripheral blood plasma were available for each subject. DNA methylation was profiled utilizing the Infinium® MethylationEPIC BeadChip (Illumina) and analysed using the RnBeads software. Significantly (FDR adjusted P < 0.05) differentially methylated probes (DMPs) between tumor and MN were identified and examined in the liquids (done at a grouped and individual subject level). Results: DNA methylation analysis of urine and blood in men with metastatic PCa showed highly correlated patterns between the different liquid types (ρ = 0.93, P < 0.0001), with large contributions from non-tumor sources. DNA methylation profiles of liquids were more similar between subjects, than intra-individual liquid-tumor correlations. Overall, both urine and plasma are viable surrogates for tumor tissue biopsies, capturing up to 39.40% and 64.14% of tumor-specific methylation alterations, respectively. Conclusion: We conclude that both urine and blood plasma are easily accessible and sensitive biofluids for the study of PCa epigenomic alterations.

36. Evaluating liquid biopsies for methylomic profiling of prostate cancer

Author

Silva, Romina, Moran, Bruce, Russell, Niamh M., Fahey, Ciara, Vlajnic, Tatjana, Rustom P. Manecksha, Finn, Stephen P., Brennan, Donal J., Gallagher, William M., and Perry, Antoinette S.

Subjects
3. Good health
Abstract

Background: Liquid biopsies offer significant potential for informing on cancer progression and therapeutic resistance via minimally invasive serial monitoring of genetic alterations. Although the cancer epigenome is a central driving force in most neoplasia, the accuracy of monitoring the tumor methylome using liquid biopsies remains relatively unknown. Objectives: to investigate how well two types of liquid biopsy (urine and blood) capture the prostate cancer methylome, and may thus serve as a non-invasive surrogate for studying the tumor epigenome. Methods: A cohort of four metastatic treatment naïve prostate cancer (PCa) patients was selected. Matched biopsy cores (tumor and histologically matched-normal), post-DRE, pre-biopsy urine, and peripheral blood plasma were available for each subject. DNA methylation was profiled utilizing the Infinium® MethylationEPIC BeadChip (Illumina) and analysed using the RnBeads software. Significantly (FDR adjusted P < 0.05) differentially methylated probes (DMPs) between tumor and MN were identified and examined in the liquids (done at a grouped and individual subject level). Results: DNA methylation analysis of urine and blood in men with metastatic PCa showed highly correlated patterns between the different liquid types (ρ = 0.93, P < 0.0001), with large contributions from non-tumor sources. DNA methylation profiles of liquids were more similar between subjects, than intra-individual liquid-tumor correlations. Overall, both urine and plasma are viable surrogates for tumor tissue biopsies, capturing up to 39.40% and 64.14% of tumor-specific methylation alterations, respectively. Conclusion: We conclude that both urine and blood plasma are easily accessible and sensitive biofluids for the study of PCa epigenomic alterations.

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