Importance: Early detection of glaucoma is essential to timely monitoring and treatment, and primary open-angle glaucoma risk can be assessed by measuring intraocular pressure (IOP) or optic nerve head vertical cup-disc ratio (VCDR). Polygenic risk scores (PRSs) could provide a link between genetic effects estimated from genome-wide association studies (GWASs) and clinical applications to provide estimates of an individual's genetic risk by combining many identified variants into a score.
Objective: To construct IOP and VCDR PRSs with clinically relevant predictive power.
Age-related cataracts is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation, and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear.
View Article and Find Full Text PDFBackground: Optical coherence tomography (OCT) is a non-invasive technique to measure retinal layer thickness, providing insights into retinal ganglion cell integrity. Studies have shown reduced retinal nerve fibre layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness in Parkinson's disease (PD) patients. However, it is unclear if there is a common genetic overlap between the macula and peripapillary estimates with PD and if the genetic risk of PD is associated with changes in ganglion cell integrity estimates in young adults.
View Article and Find Full Text PDFPurpose: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus.
Design: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.
Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations.
View Article and Find Full Text PDFAstigmatism and myopia are two common ocular refractive errors that can impact daily life, including learning and productivity. Current knowledge suggests that the etiology of these conditions is the result of a complex interplay between genetic and environmental factors. Studies in populations of European ancestry have demonstrated a higher concordance of refractive errors in monozygotic (MZ) twins compared to dizygotic (DZ) twins.
View Article and Find Full Text PDFThe recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD.
View Article and Find Full Text PDFBackground: Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of the optic nerve that leads to irreversible visual impairment. Multiple epidemiological studies suggest an association between POAG and major neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson's disease). However, the nature of the overlap between neurodegenerative disorders, brain morphology and glaucoma remains inconclusive.
View Article and Find Full Text PDFParkinson's disease (PD) is a late-onset and genetically complex neurodegenerative disorder. Here we sought to identify genes and molecular pathways underlying the associations between PD and the volume of ten brain structures measured through magnetic resonance imaging (MRI) scans. We leveraged genome-wide genetic data from several cohorts, including the International Parkinson's Disease Genomics Consortium (IPDG), the UK Biobank, the Adolescent Brain Cognitive Development (ABCD) study, the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE), the Enhancing Neuroimaging Genetics through Meta-Analyses (ENIGMA), and 23andMe.
View Article and Find Full Text PDFSamples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not.
View Article and Find Full Text PDFPurpose: To investigate the association between the apolipoprotein E () E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma.
Design: Retrospective analysis of prospective cohort data.
Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which genotypes could be determined.
Purpose: To evaluate the relationship between body mass index (BMI) and glaucoma progression.
Design: Multicohort observational study.
Methods: This study combined a retrospective longitudinal analysis of suspect and early manifest primary open angle glaucoma cases from the Progression Risk of Glaucoma: RElevant SNPs with Significant Association (PROGRESSA) study with 2 replication cohorts from the UK Biobank and the Canadian Longitudinal Study of Ageing (CLSA).
Migraine is a highly common and debilitating disorder that often affects individuals in their most productive years of life. Previous studies have identified both genetic variants and brain morphometry differences associated with migraine risk. However, the relationship between migraine and brain morphometry has not been examined on a genetic level, and the causal nature of the association between brain structure and migraine risk has not been determined.
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