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...
Autores principales: | , , , |
---|---|
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 |