Anna Neustaeter | University Medical Center Groningen (original) (raw)

Papers by Anna Neustaeter

British Journal of Ophthalmology, 2022

AimsTo build a questionnaire-based myopia proxy and to validate the proxy by confirming its assoc... more AimsTo build a questionnaire-based myopia proxy and to validate the proxy by confirming its association with educational attainment and a Polygenic Risk Score (PRS) for myopia.MethodsData were collected between 2014 and 2017 from 88 646 Dutch adults from the LifeLines Cohort. First, we performed principal component analysis (PCA) to responses of five refraction-status questions. Second, we measured the refractive state in a subset of LifeLines participants (n=326) and performed logistic regression using myopia (mean spherical equivalent

GENOME-WIDE ASSOCIATION STUDIES AND FINE MAPPING FOR SPASTIC SYNDROME IN HOLSTEIN CATTLE Anna Neu... more GENOME-WIDE ASSOCIATION STUDIES AND FINE MAPPING FOR SPASTIC SYNDROME IN HOLSTEIN CATTLE Anna Neustaeter Advisors: University of Guelph, 2015 Dr. Flavio S. Schenkel Dr. Brad Hanna (Co-advisor) This study investigated genetic contributions to North American Holsteins affected with Spastic Syndrome. The heritability estimate for the study population was 0.26. A GWAS via the generalized quasi-likelihood logistic regression on two animal cohorts genotyped with the 50k SNP panel and imputed high density SNP panel revealed six and 18 significant SNPs for the first cohort, and 98 and 522 significant SNPs for the second cohort. Significant regions were obtained on two chromosomes, with one QTL-like peak approximately 1 megabase pair (Mb) in length, and another in a QTL-like peak approximately 20 Mb in length. Functional and in silico analyses revealed seven candidate genes for both study populations. Candidate gene function involved neurons and skeletal muscle, with two genes appearing in b...

We have systematically extracted all available heritability (h 2) estimates of glaucoma and relat... more We have systematically extracted all available heritability (h 2) estimates of glaucoma and related endophenotypes from the literature and summarized the evidence by meta-analysis. Glaucoma endophenotypes were classified into 10 clusters: intraocular pressure, anterior chamber size, central corneal thickness, cup-to-disc ratio, disc size, cup size, corneal hysteresis, retinal nerve fiber layer thickness, cup shape, and peripapillary atrophy. Random-effects meta-analyses were performed for each cluster. For clusters with n ≥ 10 h 2 estimates, we also performed subgroup and meta-regression analyses. The literature search yielded 53 studies. The h 2 of primary open-angle glaucoma ranged from 0.17 to 0.81, and was 0.65 for primary angle-closure glaucoma in a single study. The pooled endophenotype h 2 estimates were

Investigative Ophthalmology & Visual Science, 2018

Investigative Ophthalmology & Visual Science, 2020

A Correction to this paper has been published: https://doi.org/10.1038/s41433-021-01511-3

BMC Ophthalmology

Background Early detection of glaucoma is paramount to maintain patients’ eyesight, however glauc... more Background Early detection of glaucoma is paramount to maintain patients’ eyesight, however glaucomatous vision loss tends to begin in the periphery with up to 50% of patients unaware they are affected. Because glaucomatous vision loss is permanent, screening appears attractive, but currently is not cost-effective. Therefore we aim to investigate the utility of genetic pre-screening for glaucoma in a population-based setting, called EyeLife. Methods EyeLife adopts a double blind prospective design with contrasting groups. Selected participants (n = 1600) from the Lifelines cohort are 55 years of age or older, and of either the highest or lowest 20% of the genetic risk distribution for glaucoma. We obtained a highly curated list of genetic variants from the literature to obtain each participants’ genetic risk for glaucoma. Participants will undergo comprehensive ophthalmic screening. The primary outcome is the relative risk of glaucoma given a high genetic risk compared to a low gene...

Investigative Opthalmology & Visual Science

We investigated relationship of glaucoma with measurements related to autonomic dysfunction, incl... more We investigated relationship of glaucoma with measurements related to autonomic dysfunction, including heart rate variability (HRV) and blood pressure (BP). METHODS. Glaucoma was defined using a questionnaire-based algorithm for 86,841 LifeLines Cohort Study participants. Baseline HRV (root mean square of successive differences [RMSSD]) was calculated from resting electrocardiograms; systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) were oscillometricbased measurements. We used a generalized linear mixed model, adjusted for age, age square, sex, body mass index, and familial relationships to assess the relationship of baseline HRV and BP (continuous and quartiles), hypertension, and antihypertensive medication with glaucoma at follow up (median, 3.8 years). RESULTS. The odds ratio (OR) of glaucoma was 0.95 (95% confidence interval [CI], 0.92-0.99) per unit increase in log-transformed RMSSD (in ms), indicating that autonomous dysfunction (low HRV) is associated with a higher risk of glaucoma. Per 10-mm Hg increase in BP, we found ORs of 1.03 (95% CI, 1.01-1.05; P = 0.015) for SBP, 1.01 (95% CI, 0.97-1.05; P = 0.55) for DBP, 1.03 (95% CI, 1.00-1.06; P = 0.083) for MAP, and 1.04 (95% CI, 1.01-1.07; P = 0.006) for PP. The OR for the lowest versus highest RMSSD quartile was 1.15 (95% CI, 1.05-1.27; P = 0.003). The ORs for the highest versus second quartile were 1.09 (95% CI, 0.99-1.19; P = 0.091) for SBP and 1.13 (95% CI, 1.02-1.24; P = 0.015) for PP. Glaucoma was more common among hypertensives (OR, 1.25; 95% CI, 1.16-1.35; P < 0.001); among those using angiotensin-converting enzyme (ACE) inhibitors (OR, 1.35; 95% CI, 1.18-1.55; P < 0.001); and among those using calcium-channel blockers (OR, 1.19; 95% CI, 1.01-1.40; P = 0.039). CONCLUSIONS. Low HRV, high SBP, high PP, and hypertension were associated with glaucoma. Longitudinal studies may elucidate if autonomic dysregulation and high BP also predict glaucoma incidence.

Eye

Purpose To improve upon self-reported glaucoma status in population-based cohorts by developing a... more Purpose To improve upon self-reported glaucoma status in population-based cohorts by developing a questionnaire-based proxy incorporating self-reported status in conjunction with glaucoma-specific visual complaints. Methods A vision specific questionnaire, including questions from the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) was administered to 79,866 Lifelines participants, a population-based cohort study in the Northern Netherlands. We compared NEI-VFQ-25 responses between 'definite' glaucoma cases (n = 90; self-reported surgical cases) and an age-and gender-matched subset of controls (n = 1,800) to uncover glaucoma-specific visual complaints, using a case-control logistic regression. We defined 'probable glaucoma' as both self-reported disease status and visual complaints, and 'possible glaucoma' as either. To evaluate the resulting proxy, we determined age-stratified glaucoma prevalences in the remaining cohort and compared the result to the literature. Results Per unit increase in the vision subscales (range 0-100) distance, peripheral and low luminance, we observed significantly increased odds of definite glaucoma (2% [P = 0.03], 4% [P = 1.2 × 10 −8 ] and 2% [P = 0.02], respectively); the associated area under the curve was 0.73. We identified 300 probable and 3,015 (1,434 by self-report) possible glaucoma cases. Standardised prevalences of definite, probable and possible glaucoma for 55+ were 0.4%, 1.1% and 7.3%, respectively. For self-reported glaucoma (combining definite, probable and possible by self-report), this was 5.2%. Conclusions The combination of self-reported glaucoma status and visual complaints can be used to capture glaucoma cases in population-based settings. The resulting prevalence of combined definite and probable glaucoma (1.5%) appears to be more consistent with previous reports than the prevalence estimate of 5.2% based only on self-report.

Survey of Ophthalmology

We have systematically extracted all available heritability (h2) estimates of glaucoma and relate... more We have systematically extracted all available heritability (h2) estimates of glaucoma and related endophenotypes from the literature, and summarize the evidence by meta-analysis. Glaucoma endophenotypes were classified into 10 clusters: intraocular pressure (IOP), anterior chamber size (ACS), central corneal thickness (CCT), cup-to-disc ratio (CDR), disc size (DS), cup size (CS), corneal hysteresis (CH), retinal nerve fiber layer thickness (RNFLT), cup shape (CSH), and peripapillary atrophy (PPA). Random-effects meta-analyses were performed for each cluster. For clusters with n ≥10 h2 estimates, we also performed subgroup and meta-regression analyses. The literature search yielded 53 studies. The h2 of primary open-angle glaucoma ranged from 0.17 to 0.81, and was 0.65 for primary angle-closure glaucoma in a single study. The pooled endophenotype h2 estimates were: IOP: 0.43(0.38-0.48), ACS: 0.67(0.60-0.74), CCT: 0.81(0.73-0.87), CDR: 0.56(0.44-0.68), DS: 0.61(0.37-0.81), CS: 0.58(0.35-0.78), CH: 0.40(0.29-0.51), RNFLT: 0.73(0.42-0.91), CS: 0.62(0.22-0.90), and PPA: 0.73(0.70-0.75). We identified mean age, ethnicity, and study design as major sources of heterogeneity. Our results confirm the strong influence of genetic factors on glaucoma and its endophenotypes. These pooled h2 estimates provide the most accurate assessment to date of the total genetic variation that can ultimately be explained by gene-finding studies.

BMJ Open

IntroductionGlaucoma is the second leading cause of age-related vision loss worldwide; it is an u... more IntroductionGlaucoma is the second leading cause of age-related vision loss worldwide; it is an umbrella term that is used to describe a set of complex ocular disorders with a multifactorial aetiology. Both genetic and lifestyle risk factors for glaucoma are well established. Thus far, however, systematic reviews on the heritability of glaucoma have focused on the heritability of primary open-angle glaucoma only. No systematic review has comprehensively reviewed or meta-analysed the heritability of other types of glaucoma, including glaucoma-related endophenotypes. The aim of this study will be to identify relevant scientific literature regarding the heritability of both glaucoma and related endophenotypes and summarise the evidence by performing a systematic review and meta-analysis.Methods and analysisThis systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist, which provides a standardised approach for carrying...