ORCID Profile
0000-0002-1987-8900
Current Organisation
University of Southampton
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Publisher: Hindawi Limited
Date: 29-06-2021
DOI: 10.1002/HUMU.24242
Publisher: Springer Science and Business Media LLC
Date: 06-01-2013
DOI: 10.1038/NG.2506
Publisher: Springer Science and Business Media LLC
Date: 12-09-2010
DOI: 10.1038/NG.661
Publisher: Oxford University Press (OUP)
Date: 13-01-2012
DOI: 10.1093/IJE/DYR204
Publisher: Springer Science and Business Media LLC
Date: 22-09-2014
DOI: 10.1038/NCOMMS5883
Abstract: Glaucoma is characterized by irreversible optic nerve degeneration and is the most frequent cause of irreversible blindness worldwide. Here, the International Glaucoma Genetics Consortium conducts a meta-analysis of genome-wide association studies of vertical cup-disc ratio (VCDR), an important disease-related optic nerve parameter. In 21,094 in iduals of European ancestry and 6,784 in iduals of Asian ancestry, we identify 10 new loci associated with variation in VCDR. In a separate risk-score analysis of five case-control studies, Caucasians in the highest quintile have a 2.5-fold increased risk of primary open-angle glaucoma as compared with those in the lowest quintile. This study has more than doubled the known loci associated with optic disc cupping and will allow greater understanding of mechanisms involved in this common blinding condition.
Publisher: American Medical Association (AMA)
Date: 20-11-0200
Publisher: Wiley
Date: 31-07-2020
DOI: 10.1002/PATH.5506
Publisher: Elsevier BV
Date: 07-2023
Publisher: Oxford University Press (OUP)
Date: 22-03-2011
DOI: 10.1093/HMG/DDR120
Abstract: Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a meta-analysis using data from six independent studies including: the Rotterdam Study (n= 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n= 1750), Amsterdam Glaucoma Study (n= 296) and cohorts from Erlangen and Tübingen (n= 1363), South ton (n= 702) and deCODE (n= 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P= 1.41 × 10(-8)) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3 and SALL1 (both P= 0.04) with glaucoma. In conclusion, we found consistent evidence for three common variants (CDKN2B, ATOH7 and SIX1) significantly associated with glaucoma. These findings may shed new light on the pathophysiological protein pathways leading to glaucoma, and point to pathways involved in the growth and development of the optic nerve.
Publisher: Springer Science and Business Media LLC
Date: 27-11-2019
DOI: 10.1038/S42003-019-0634-9
Abstract: A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG) intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is h ered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH.
Publisher: Springer Science and Business Media LLC
Date: 20-01-2020
Publisher: Public Library of Science (PLoS)
Date: 25-01-2018
Publisher: Oxford University Press (OUP)
Date: 10-01-2017
DOI: 10.1093/HMG/DDW399
Publisher: National Institute for Health and Care Research
Date: 2021
DOI: 10.3310/EME08020
Abstract: In chronic central serous chorioretinopathy, fluid accumulates in the subretinal space and causes permanent vision loss in ≈ 30% of patients. There is no definitive treatment. Previous research suggests that the mineralocorticoid receptor antagonist eplerenone is effective but it is not licensed for chronic central serous chorioretinopathy. The objective was to evaluate whether or not eplerenone was safe and superior to placebo for treating chronic central serous chorioretinopathy. We also aimed to set up a biobank of DNA, serum and plasma s les from treatment-naive participants for future research. The trial was a parallel, randomised (1 : 1 ratio), multicentre, double-masked, placebo-controlled superiority trial comparing eplerenone plus usual care with placebo plus usual care. Participants were randomly allocated to eplerenone or placebo using a secure online system that returned a unique number corresponding to a bottle of the investigational medicinal product. Participants, clinical care teams, pharmacists, outcome assessors and the trial management group were masked. The trial took place in 22 NHS hospitals in the UK. Eligible participants were patients aged 18–60 years with treatment-naive chronic central serous chorioretinopathy of at least 4 months’ duration, a best corrected visual acuity score of 54–85 letters and no other conditions affecting visual acuity or contraindications to taking eplerenone or placebo. The intervention was oral eplerenone (25 mg/day for 1 week, increased to 50 mg/day for up to 12 months). Placebo was a lactose-filled capsule that appeared identical to the overencapsulated eplerenone tablets. To maintain blinding, participants in the placebo group followed the same dose escalation schedule as the eplerenone group. Usual care was included in both groups and was administered at the discretion of clinicians. The primary outcome was best corrected visual acuity score at 12 months. Secondary outcomes were low-luminance visual acuity, central subfield retinal thickness, change in subretinal fluid thickness, systemic and ocular adverse events, macular atrophy of the retinal pigment epithelium, subfoveal choroidal thickness, choroidal permeability, resolution of subretinal fluid, time to recurrence of subretinal fluid, fundus fluorescein angiography phenotype, incidence of chronic central serous chorioretinopathy in the fellow eye, and patient-reported visual function. Between 11 January 2017 and 22 February 2018, 57 participants were randomised to eplerenone and 57 to placebo 57 and 54 participants, respectively, were included in the analysis of the primary outcome. The modelled mean best corrected visual acuity score at 12 months in the eplerenone and placebo groups was 80.4 letters (standard deviation 4.6 letters) and 79.5 letters (standard deviation 4.5 letters), with an estimated difference between groups of 1.73 letters (95% confidence interval –1.12 to 4.57 letters p = 0.24). Hyperkalaemia occurred in eight participants in each group (14%). No serious adverse events occurred in the eplerenone group three unrelated serious adverse events occurred in the placebo group. Limitations included the inability to prevent co-treatments and discontinuation of the investigational medicinal product in the event of resolution or hyperkalaemia. Eplerenone was safe but not superior to placebo in improving best corrected visual acuity in people with chronic central serous chorioretinopathy during 12 months of follow-up. In future work, ophthalmologists should investigate alternative treatments for this condition, which remains complicated to treat. Current Controlled Trials ISRCTN92746680. This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation Vol. 8, No. 2. See the NIHR Journals Library website for further project information.
Publisher: Springer Science and Business Media LLC
Date: 21-12-2015
DOI: 10.1038/NG.3448
Publisher: Springer Science and Business Media LLC
Date: 24-02-2021
DOI: 10.1038/S41467-020-20851-4
Abstract: Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638 , CLIC5, SLC2A12, YAP1, MXRA5 , and SMAD6 . Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Angela Cree.