Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Investigating the Genetic Background of Spastic Syndrome in North American Holstein Cattle Based on Heritability, Genome-Wide Association, and Functional Genomic Analyses.

Spastic syndrome is a chronic, progressive disorder of adult cattle characterized by episodes of sudden involuntary muscle contractions or spasms of the extensor and abductor muscles of one or both hind limbs. In this study, a case-control genome-wide association study (GWAS) was performed on an adult Holstein cattle cohort. Based on the 50 K and high-density (HD) SNP panel GWAS, we identified 98 and 522 SNPs, respectively.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

Objective: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.

Design: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284).

Mediterranean-Like Dietary Pattern Associations With Gut Microbiome Composition and Subclinical Gastrointestinal Inflammation.

Background & Aims: Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation.

Development and validation of a questionnaire-based myopia proxy in adults: the LifeLines Cohort Study.

Aims: To 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.

Methods: Data 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.

Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife).

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.

Autonomic Dysfunction and Blood Pressure in Glaucoma Patients: The Lifelines Cohort Study.

Purpose: 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 oscillometric-based measurements.

Glaucoma in large-scale population-based epidemiology: a questionnaire-based proxy.

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.

Associations between tinnitus and glaucoma suggest a common mechanism: A clinical and population-based study.

The purpose of this study was to determine if there is an association between tinnitus and glaucoma. We tested this by first completing a clinic-based cross-sectional questionnaire study in which we sent a series of tinnitus-related questions to glaucoma patients and healthy subjects, and then followed up with a large population-based cross-sectional study in which glaucoma and tinnitus were also assessed by questionnaire. For the clinical study, we received 209 responses from glaucoma patients and 109 responses from healthy subjects (primarily the spouses of the patients).

Heritability of glaucoma and glaucoma-related endophenotypes: Systematic review and meta-analysis.

We have systematically extracted all available heritability (h) 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.

Heritability of glaucoma and glaucoma-related endophenotypes: systematic review and meta-analysis protocol.

Introduction: Glaucoma 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.