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Article ; Online: Maternal immune activation induces methylation changes in schizophrenia genes.

Johnson, Thomas / Saatci, Defne / Handunnetthi, Lahiru

2022 Volume 17, Issue 11, Page(s) e0278155

Abstract: Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could ... ...

Abstract	Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.
MeSH term(s)	Adult ; Female ; Pregnancy ; Humans ; Methylation ; Schizophrenia/genetics ; Family ; Protein Processing, Post-Translational ; Brain
Language	English
Publishing date	2022-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0278155
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Maternal immune activation induces methylation changes in schizophrenia genes

Thomas Johnson / Defne Saatci / Lahiru Handunnetthi

PLoS ONE, Vol 17, Iss

2022 Volume 11

Abstract	Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Maternal infection in gestation increases the risk of non-affective psychosis in offspring: a meta-analysis.

Saatci, Defne / van Nieuwenhuizen, Adrienne / Handunnetthi, Lahiru

Journal of psychiatric research

2021 Volume 139, Page(s) 125–131

Abstract: Maternal infection is thought to increase the risk of non-affective psychosis including schizophrenia. However, observational studies have produced conflicting results and little is known about the importance of timing of infection in mediating ... ...

Abstract	Maternal infection is thought to increase the risk of non-affective psychosis including schizophrenia. However, observational studies have produced conflicting results and little is known about the importance of timing of infection in mediating subsequent risk. In this study, we carried out a meta-analysis of observational studies to investigate the risk of maternal infection and subsequent risk of non-affective psychosis. Using seven cohort studies, we found that maternal infection during gestation increased the risk of non-affective psychosis [relative risk (RR): 1.28 (95% CI:1.05-1.57, p = 0.02, I
MeSH term(s)	Cohort Studies ; Female ; Humans ; Observational Studies as Topic ; Pregnancy ; Psychotic Disorders/epidemiology ; Psychotic Disorders/etiology ; Risk Factors ; Schizophrenia/epidemiology
Language	English
Publishing date	2021-05-23
Publishing country	England
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
ZDB-ID	3148-3
ISSN	1879-1379 ; 0022-3956
ISSN (online)	1879-1379
ISSN	0022-3956
DOI	10.1016/j.jpsychires.2021.05.039
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Article ; Online: Childhood, teenage and young adult cancer diagnosis during the first wave of the COVID-19 pandemic: a population-based observational cohort study in England.

Saatci, Defne / Oke, Jason / Harnden, Anthony / Hippisley-Cox, Julia

Archives of disease in childhood

2022 Volume 107, Issue 8, Page(s) 740–746

Abstract: Objective: To investigate childhood, teenage and young adult cancer diagnostic pathways during the first wave of the COVID-19 pandemic in England.: Design: Population-based cohort study.: Setting and participants: QResearch, a nationally ... ...

Abstract	Objective: To investigate childhood, teenage and young adult cancer diagnostic pathways during the first wave of the COVID-19 pandemic in England. Design: Population-based cohort study. Setting and participants: QResearch, a nationally representative primary care database, linked to hospital admission, mortality and cancer registry data, was used to identify childhood, teenage and young adult cancers (0-24 years) diagnosed between 1 January 2017 and 15 August 2020. Main outcomes: Main outcomes of interest were: (1) number of incident cancer diagnoses per month, (2) diagnostic, treatment time intervals and (3) cancer-related intensive care admissions. Results: 2607 childhood, teenage and young adult cancers were diagnosed from 1 January 2017 to 15 August 2020; 380 were diagnosed during the pandemic period. Overall, 17% (95% CI -28.0% to -4.0%) reduction in the incidence rate ratio of cancers was observed during the pandemic. Specific decreases were seen for central nervous system tumour (-38% (95% CI -52% to -21%)) and lymphoma (-28% (95% CI -45% to -5%)) diagnoses. Additionally, childhood cancers diagnosed during the pandemic were significantly more likely to have intensive care admissions (adjusted OR 2.2 (95% CI 1.33 to 3.47)). Median time-to-diagnosis did not significantly differ across periods (+4.5 days (95% CI -20.5 to +29.5)), while median time-to-treatment was shorter during the pandemic (-0.7 days (95% CI -1.1 to -0.3)). Conclusions: Collectively, our findings of a significant reduction in cancer diagnoses and increase in intensive care admissions provide initial insight into the changes that occurred to childhood, teenage and young adult cancer diagnostic pathways during the first wave of the pandemic.
MeSH term(s)	Adolescent ; COVID-19/diagnosis ; COVID-19/epidemiology ; Child ; Cohort Studies ; Humans ; Incidence ; Neoplasms/diagnosis ; Neoplasms/epidemiology ; Neoplasms/etiology ; Pandemics ; Young Adult
Language	English
Publishing date	2022-03-22
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	524-1
ISSN	1468-2044 ; 0003-9888 ; 1359-2998
ISSN (online)	1468-2044
ISSN	0003-9888 ; 1359-2998
DOI	10.1136/archdischild-2021-322644
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Article ; Online: Maternal immune activation downregulates schizophrenia genes in the foetal mouse brain.

Handunnetthi, Lahiru / Saatci, Defne / Hamley, Joseph C / Knight, Julian C

Brain communications

2021 Volume 3, Issue 4, Page(s) fcab275

Abstract: Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune ... ...

Abstract	Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Maternal immune activation by infections during pregnancy is hypothesized to be a key environmental risk factor. However, little is known about how maternal immune activation contributes to schizophrenia pathogenesis. In this study, we investigated if maternal immune activation influences the expression of genes associated with schizophrenia in foetal mouse brains. We found that two sets of schizophrenia genes were downregulated more than expected by chance in the foetal mouse brain following maternal immune activation, namely those genes associated with schizophrenia through genome-wide association study (fold change = 1.93, false discovery rate = 4 × 10
Language	English
Publishing date	2021-11-15
Publishing country	England
Document type	Journal Article
ISSN	2632-1297
ISSN (online)	2632-1297
DOI	10.1093/braincomms/fcab275
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Article ; Online: The role of latitude and infections in the month-of-birth effect linked to schizophrenia.

Saatci, Defne / Johnson, Thomas / Smee, Madeleine / van Nieuwenhuizen, Adrienne / Handunnetthi, Lahiru

Brain, behavior, & immunity - health

2022 Volume 24, Page(s) 100486

Abstract: There is an intriguing association between winter births and subsequent increased risk of schizophrenia. However, little is known about the environmental risk factors that contribute this month-of-birth effect. The aims of this study were to carry out a ... ...

Abstract	There is an intriguing association between winter births and subsequent increased risk of schizophrenia. However, little is known about the environmental risk factors that contribute this month-of-birth effect. The aims of this study were to carry out a systematic review and meta-analysis of studies investigating the month-of-birth effect in schizophrenia and to explore possible factors such as latitude, daylight and infections that could explain this epidemiological observation. Medline, Embase and the Cochrane Library were searched for articles published up to December 23, 2021. Study selection, data extraction and analysis were undertaken according to Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Generic inverse-variance with random effects models were used to determine the risk ratios (RR) and 95% confidence intervals (CI) for each month-of-birth. Associations between variables latitude and daylight were investigated using linear regression and Kendall's rank correlation coefficients were calculated assess the relationship between monthly infections rates schizophrenia births. Ten studies were included in the meta-analysis encompassing 262,188 schizophrenia patients. We identified significantly higher number of schizophrenia births in December [1.04 (95%CI 1.00-1.08)], January [1.06 (95%CI 1.03-1.1)] and February [1.03 (95%CI 1.00-1.05)]. We did not find any association between latitude and the magnitude of the month-of-birth effect. On the other hand, we found a significant negative correlation between monthly severe enterovirus cases and schizophrenia births (tau -0.57, p = 0.0099) using data from Taiwan. This highlights a role for enterovirus infections in mediating the month-of-birth effect in schizophrenia and these results carry implications for disease prevention strategies.
Language	English
Publishing date	2022-07-06
Publishing country	United States
Document type	Journal Article
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2022.100486
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Article ; Online: Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study.

Clift, Ashley Kieran / Saatci, Defne / Coupland, Carol A C / Dambha-Miller, Hajira / Hippisley-Cox, Julia

Annals of internal medicine

2021 Volume 174, Issue 10, Page(s) 1483–1487

MeSH term(s)	Adolescent ; Adult ; Aged ; Anemia, Sickle Cell/complications ; COVID-19/complications ; COVID-19/mortality ; Child ; Child, Preschool ; Female ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; SARS-CoV-2 ; Young Adult
Language	English
Publishing date	2021-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M21-1375
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Article ; Online: Abdominal migraine.

Angus-Leppan, Heather / Saatci, Defne / Sutcliffe, Alastair / Guiloff, Roberto J

BMJ (Clinical research ed.)

2018 Volume 360, Page(s) k179

MeSH term(s)	Diagnosis, Differential ; Humans ; Migraine Disorders/diagnosis ; Migraine Disorders/prevention & control ; Risk Factors
Language	English
Publishing date	2018--19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj.k179
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Article ; Online: Ethnic disparities in COVID-19 outcomes: a multinational cohort study of 20 million individuals from England and Canada.

Zaccardi, Francesco / Tan, Pui San / Shah, Baiju R / Everett, Karl / Clift, Ash Kieran / Patone, Martina / Saatci, Defne / Coupland, Carol / Griffin, Simon J / Khunti, Kamlesh / Dambha-Miller, Hajira / Hippisley-Cox, Julia

BMC public health

2023 Volume 23, Issue 1, Page(s) 399

Abstract: Background: Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts ...

Abstract	Background: Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outcomes. Methods: We identified adults aged 18 to 99 years in the QResearch primary care (England) and Ontario (Canada) healthcare administrative population-based datasets (start of follow-up: 24th and 25th Jan 2020 in England and Canada, respectively; end of follow-up: 31st Oct and 30th Sept 2020, respectively). We harmonised the definitions and the design of two cohorts to investigate associations between ethnicity and COVID-19-related death, hospitalisation, and intensive care (ICU) admission, adjusted for confounders, and combined the estimates obtained from survival analyses. We calculated the 'percentage of excess risk mediated' by these risk factors in the QResearch cohort. Results: There were 9.83 million adults in the QResearch cohort (11,597 deaths; 21,917 hospitalisations; 2932 ICU admissions) and 10.27 million adults in the Ontario cohort (951 deaths; 5132 hospitalisations; 1191 ICU admissions). Compared to the general population, pooled random-effects estimates showed that South Asian ethnicity was associated with an increased risk of COVID-19 death (hazard ratio: 1.63, 95% CI: 1.09-2.44), hospitalisation (1.53; 1.32-1.76), and ICU admission (1.67; 1.23-2.28). Associations with ethnic groups were consistent across levels of deprivation. In QResearch, sociodemographic, lifestyle, and clinical factors accounted for 42.9% (South Asian) and 39.4% (Black) of the excess risk of COVID-19 death. Conclusion: International population-level analyses demonstrate clear ethnic inequalities in COVID-19 risks. Policymakers should be cognisant of the increased risks in some ethnic populations and design equitable health policy as the pandemic continues.
MeSH term(s)	Adult ; Humans ; Cohort Studies ; COVID-19 ; SARS-CoV-2 ; Ontario/epidemiology ; England/epidemiology
Language	English
Publishing date	2023-02-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041338-5
ISSN	1471-2458 ; 1471-2458
ISSN (online)	1471-2458
ISSN	1471-2458
DOI	10.1186/s12889-023-15223-8
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Article ; Online: Ethnicity and risks of severe COVID-19 outcomes associated with glucose-lowering medications: A cohort study.

Zaccardi, Francesco / Tan, Pui San / Coupland, Carol / Shah, Baiju R / Clift, Ash Kieran / Saatci, Defne / Patone, Martina / Griffin, Simon J / Dambha-Miller, Hajira / Khunti, Kamlesh / Hippisley-Cox, Julia

Diabetes, obesity & metabolism

2022 Volume 25, Issue 2, Page(s) 611–617

MeSH term(s)	Humans ; Cohort Studies ; COVID-19/complications ; Glucose ; Ethnicity ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy
Chemical Substances	Glucose (IY9XDZ35W2)
Language	English
Publishing date	2022-09-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.14872
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