Cargando…

Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration

A subset of ophthalmic imaging examination results from 334 patients were subjected to reanalysis to identify a specific group of patients with pigment epithelial detachment (PED) in at least one eye. Overall, we found a subgroup of 47 patients manifesting PED and studied their genotypes in comparis...

Descripción completa

Detalles Bibliográficos
Autores principales: Wąsowska, Anna, Sendecki, Adam, Boguszewska-Chachulska, Anna, Teper, Sławomir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531282/
https://www.ncbi.nlm.nih.gov/pubmed/37761846
http://dx.doi.org/10.3390/genes14091707
_version_ 1785111682097348608
author Wąsowska, Anna
Sendecki, Adam
Boguszewska-Chachulska, Anna
Teper, Sławomir
author_facet Wąsowska, Anna
Sendecki, Adam
Boguszewska-Chachulska, Anna
Teper, Sławomir
author_sort Wąsowska, Anna
collection PubMed
description A subset of ophthalmic imaging examination results from 334 patients were subjected to reanalysis to identify a specific group of patients with pigment epithelial detachment (PED) in at least one eye. Overall, we found a subgroup of 47 patients manifesting PED and studied their genotypes in comparison to those of patients with age-related macular degeneration without PED and healthy controls. We established a polygenic risk score that allowed the explanation of 16.3% of the variation within the disease. The highest predictive value was achieved for a model consisting of six non-coding variants: rs760306 (BEST1), rs148662546 (BEST1), rs11569560 (C3), rs74600252 (GUCA1B), rs2240688 (PROM1), and rs185507582 (TCF4). The risk of PED occurrence was found to be the highest in the first tercile, showing a 7.89-fold higher risk compared to the third tercile for AMD without PED (95% CI: 2.87; 21.71, p < 0.001) and a 7.22-fold higher risk compared to the healthy controls (95% CI: 2.60; 20.06, p < 0.001). In addition, we focused on rare variants in targeted genes. The rare variants’ burden was compared among the groups, but no statistical significance was observed in the number of rare variants, predicted functional effects, or pathogenicity classification.
format Online
Article
Text
id pubmed-10531282
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105312822023-09-28 Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration Wąsowska, Anna Sendecki, Adam Boguszewska-Chachulska, Anna Teper, Sławomir Genes (Basel) Article A subset of ophthalmic imaging examination results from 334 patients were subjected to reanalysis to identify a specific group of patients with pigment epithelial detachment (PED) in at least one eye. Overall, we found a subgroup of 47 patients manifesting PED and studied their genotypes in comparison to those of patients with age-related macular degeneration without PED and healthy controls. We established a polygenic risk score that allowed the explanation of 16.3% of the variation within the disease. The highest predictive value was achieved for a model consisting of six non-coding variants: rs760306 (BEST1), rs148662546 (BEST1), rs11569560 (C3), rs74600252 (GUCA1B), rs2240688 (PROM1), and rs185507582 (TCF4). The risk of PED occurrence was found to be the highest in the first tercile, showing a 7.89-fold higher risk compared to the third tercile for AMD without PED (95% CI: 2.87; 21.71, p < 0.001) and a 7.22-fold higher risk compared to the healthy controls (95% CI: 2.60; 20.06, p < 0.001). In addition, we focused on rare variants in targeted genes. The rare variants’ burden was compared among the groups, but no statistical significance was observed in the number of rare variants, predicted functional effects, or pathogenicity classification. MDPI 2023-08-27 /pmc/articles/PMC10531282/ /pubmed/37761846 http://dx.doi.org/10.3390/genes14091707 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wąsowska, Anna
Sendecki, Adam
Boguszewska-Chachulska, Anna
Teper, Sławomir
Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title_full Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title_fullStr Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title_full_unstemmed Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title_short Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration
title_sort polygenic risk score and rare variant burden identified by targeted sequencing in a group of patients with pigment epithelial detachment in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531282/
https://www.ncbi.nlm.nih.gov/pubmed/37761846
http://dx.doi.org/10.3390/genes14091707
work_keys_str_mv AT wasowskaanna polygenicriskscoreandrarevariantburdenidentifiedbytargetedsequencinginagroupofpatientswithpigmentepithelialdetachmentinagerelatedmaculardegeneration
AT sendeckiadam polygenicriskscoreandrarevariantburdenidentifiedbytargetedsequencinginagroupofpatientswithpigmentepithelialdetachmentinagerelatedmaculardegeneration
AT boguszewskachachulskaanna polygenicriskscoreandrarevariantburdenidentifiedbytargetedsequencinginagroupofpatientswithpigmentepithelialdetachmentinagerelatedmaculardegeneration
AT tepersławomir polygenicriskscoreandrarevariantburdenidentifiedbytargetedsequencinginagroupofpatientswithpigmentepithelialdetachmentinagerelatedmaculardegeneration