ORCID Profile
0000-0002-2394-5299
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 05-04-2016
DOI: 10.1038/MP.2016.45
Publisher: Cold Spring Harbor Laboratory
Date: 07-09-2019
DOI: 10.1101/755280
Abstract: To explore sex differences in the associations between arterial stiffness index, carotid intima-media thickness, white matter hyperintensities, depression and cognition. UK Biobank is a population-based cohort study of 502,664 healthy community dwelling adults aged 37-73 years. A select number of participants were recalled to participate in an online reassessment and imaging study, both of which included repeat cognitive assessments. A total of 7,394 volunteers aged 45-73 years (55% female) participated in the imaging visit and completed the self-report mental health questionnaire in the online follow-up were included in the analyses reported here. The main outcome measure of depression was measured using the PHQ-9 and cognition was assessed through measures of reaction time, verbal-numeric reasoning and visual memory. Pulse wave velocity (PWV) was assessed non-invasively using finger photoplethysmography, carotid intima-media thickness (CIMT) with automated ultrasound, and white matter hyperintensity volume with combined T1 and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. We report sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing. Section 1: What is already known on this topic Arterial stiffness and carotid intima-media thickness are two non-invasive vascular ageing markers that have been shown to be associated with depression, cognitive impairment and dementia. Some studies report sex differences in arterial stiffness and carotid intima-media thickness. There is, however, a paucity of research on sex differences in the associations between these vascular ageing markers, white matter hyperintensities, depression and cognition. Section 2: What this study adds Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. Our findings add to the existing evidence base of sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.OPHTHA.2019.08.015
Abstract: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. Cross-sectional study. We included 42 044 participants in the UK Biobank. The mean age was 56 years. Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Thicknesses of mRNFL, GCC, and GCIPL. We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30] P = 1.1×10 The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.
Publisher: Oxford University Press (OUP)
Date: 22-11-2018
Publisher: Cold Spring Harbor Laboratory
Date: 04-04-2018
DOI: 10.1101/294629
Abstract: Late-onset Alzheimer’s disease (LOAD, onset age 60 years) is the most prevalent dementia in the elderly 1 , and risk is partially driven by genetics 2 . Many of the loci responsible for this genetic risk were identified by genome-wide association studies (GWAS) 3–8 . To identify additional LOAD risk loci, the we performed the largest GWAS to date (89,769 in iduals), analyzing both common and rare variants. We confirm 20 previous LOAD risk loci and identify four new genome-wide loci ( IQCK , ACE , ADAM10 , and ADAMTS1 ). Pathway analysis of these data implicates the immune system and lipid metabolism, and for the first time tau binding proteins and APP metabolism. These findings show that genetic variants affecting APP and Aβ processing are not only associated with early-onset autosomal dominant AD but also with LOAD. Analysis of AD risk genes and pathways show enrichment for rare variants ( P = 1.32 × 10 −7 ) indicating that additional rare variants remain to be identified.
Publisher: American Medical Association (AMA)
Date: 12-2015
Publisher: BMJ
Date: 02-2019
DOI: 10.1136/BMJOPEN-2018-025077
Abstract: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc–macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and s le collection will be performed in subsets of 25 000 participants every 2–3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.
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: Elsevier BV
Date: 04-2016
Publisher: Oxford University Press (OUP)
Date: 13-06-2017
DOI: 10.1093/AJE/KWX149
Publisher: American Medical Association (AMA)
Date: 02-2019
Publisher: Springer Science and Business Media LLC
Date: 28-05-2018
Publisher: Wiley
Date: 30-03-2016
DOI: 10.1002/ANA.24621
Publisher: Cold Spring Harbor Laboratory
Date: 25-03-2019
DOI: 10.1101/582155
Abstract: The Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 in iduals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform (UKSeRP) infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 in idual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Project are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Publisher: Springer Science and Business Media LLC
Date: 26-01-2016
DOI: 10.1038/MP.2015.225
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.OPHTHA.2015.11.009
Abstract: To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study. Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data. Adults from the United Kingdom aged 40 to 69 years. Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS] Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (<0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty. Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields. The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) μm, with 95% confidence limits of 220.8 and 311.5 μm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P < 0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia. We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
DOI: 10.1007/S10654-020-00633-4
Abstract: The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 in iduals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 in idual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Publisher: Cambridge University Press (CUP)
Date: 21-10-2015
DOI: 10.1016/J.EURPSY.2015.08.006
Abstract: This study investigated differences in cognitive performance between middle-aged adults with and without a lifetime history of mood disorder features, adjusting for a range of potential confounders. Cross-sectional analysis of baseline data from the UK Biobank cohort. Adults aged 40–69 ( n = 143,828) were assessed using measures of reasoning, reaction time and memory. Self-reported data on lifetime features of major depression and bipolar disorder were used to construct groups for comparison against controls. Regression models examined the association between mood disorder classification and cognitive performance, adjusting for sociodemographic, lifestyle and clinical confounders. Inverse associations between lifetime history of bipolar or severe recurrent depression features and cognitive performance were attenuated or reversed after adjusting for confounders, including psychotropic medication use and current depressive symptoms. Participants with a lifetime history of single episode or moderate recurrent depression features outperformed controls to a small (but statistically significant) degree, independent of adjustment for confounders. There was a significant interaction between use of psychotropic medication and lifetime mood disorder features, with reduced cognitive performance observed in participants taking psychotropic medication. In this general population s le of adults in middle age, lifetime features of recurrent depression or bipolar disorder were only associated with cognitive impairment within unadjusted analyses. These findings underscore the importance of adjusting for potential confounders when investigating mood disorder-related cognitive function.
Publisher: Springer Science and Business Media LLC
Date: 15-08-2019
Publisher: Springer Science and Business Media LLC
Date: 19-03-2020
DOI: 10.1038/S42003-020-0802-Y
Abstract: Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 in iduals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11 / FBLN2 rs2630445, RBP3 rs11204213) others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Elsevier BV
Date: 10-2019
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Gallacher.