Genome-wide association study and polygenic risk scores of retinal thickness across the cognitive continuum: data from the NORFACE cohort

• Published in: Alzheimer's research & therapy Vol. 16; no. 1; pp. 38 - 14
• Main Authors: Sáez, María Eugenia, García-Sánchez, Ainhoa, de Rojas, Itziar, Alarcón-Martín, Emilio, Martínez, Joan, Cano, Amanda, García-González, Pablo, Puerta, Raquel, Olivé, Clàudia, Capdevila, Maria, García-Gutiérrez, Fernando, Castilla-Martí, Miguel, Castilla-Martí, Luis, Espinosa, Ana, Alegret, Montserrat, Ricciardi, Mario, Pytel, Vanesa, Valero, Sergi, Tárraga, Lluís, Boada, Mercè, Ruiz, Agustín, Marquié, Marta
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16-02-2024; BioMed Central; BMC
• Subjects: Alzheimer's disease; Alzheimer’s disease (AD); Biobanks; Biomarkers; Cognition & reasoning; Cognitive ability; Datasets; Dementia; Diagnosis; Disease; Gene loci; Genetic aspects; Genome-wide association studies; Genome-wide association study (GWAS); Genomes; Genomics; Health care; Measurement; Medical examination; Mendelian randomization (MR); Neurological research; Neuropathology; Neuropsychology; NORFACE; Ophthalmology; Optical coherence tomography (OCT); Optics; Polygenic risk score (PRS); Retina; Risk factors; Single nucleotide polymorphisms; Software; Tomography; Visual acuity; Spain; United Kingdom > UK; Genome-wide association study (GWAS); Alzheimer’s disease (AD); Mendelian randomization (MR); NORFACE; GR@CE; Polygenic risk score (PRS); Optical coherence tomography (OCT)
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-024-01398-8

Several studies have reported a relationship between retinal thickness and dementia. Therefore, optical coherence tomography (OCT) has been proposed as an early diagnosis method for Alzheimer's disease (AD). In this study, we performed a genome-wide association study (GWAS) aimed at identifying genes associated with retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GCIPL) thickness assessed by OCT and exploring the relationships between the spectrum of cognitive decline (including AD and non-AD cases) and retinal thickness.
RNFL and GCIPL thickness at the macula were determined using two different OCT devices (Triton and Maestro). These determinations were tested for association with common single nucleotide polymorphism (SNPs) using adjusted linear regression models and combined using meta-analysis methods. Polygenic risk scores (PRSs) for retinal thickness and AD were generated.
Several genetic loci affecting retinal thickness were identified across the genome in accordance with previous reports. The genetic overlap between retinal thickness and dementia, however, was weak and limited to the GCIPL layer; only those observable with all-type dementia cases were considered.
Our study does not support the existence of a genetic link between dementia and retinal thickness.