Related Experiment Video
Updated: May 23, 2025
A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging
Published on: July 14, 2016
Genetic Distinctions Between Reticular Pseudodrusen and Drusen: A Genome-Wide Association Study
Roy Schwartz1, Alasdair N Warwick2, Anthony P Khawaja3
1From the Moorfields Eye Hospital NHS Foundation Trust (R.S., A.N.W., H.K., S.P., M.J., C.E., A.T.), London, UK; Institute of Health Informatics (R.S.), University College London, London, UK.
Objective:
To identify genetic determinants specific to reticular pseudodrusen (RPD) compared with drusen.
Design:
Genome-wide association study (GWAS) SUBJECTS: Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort.
Methods:
Participants with RPD, drusen, and controls from the UK Biobank (UKBB), a large, multisite, community-based cohort, were included. A deep learning framework analyzed 169,370 optical coherence tomography (OCT) volumes to identify cases and controls within the UKBB. Five retina specialists validated the cohorts using OCT and color fundus photographs. Several GWAS were undertaken utilizing the quantity and presence of RPD and drusen. Genome-wide significance was defined as P < 5e-8.
Main Outcomes Measures:
Genetic associations were examined with the number of RPD and drusen within 'pure' cases, where only RPD or drusen were present in either eye. A candidate approach assessed 46 previously known AMD loci. Secondary GWAS were conducted for number of RPD and drusen in mixed cases, and binary case-control analyses for pure RPD and pure drusen.
Results:
The study included 1787 participants: 1037 controls, 361 pure drusen, 66 pure RPD, and 323 mixed cases. The primary pure RPD GWAS identified four genome-wide significant loci: rs11200630 near ARMS2-HTRA1 (P = 1.9e-09), rs79641866 at PARD3B (P = 1.3e-08), rs143184903 near ITPR1 (P = 8.1e-09), and rs76377757 near SLN (P = 4.3e-08). The latter three are uncommon variants (minor allele frequency <5%). A significant association at the CFH locus was also observed using a candidate approach (P = 1.8e-04). For pure drusen, two loci reached genome-wide significance: rs10801555 at CFH (P = 6.0e-33) and rs61871744 at ARMS2-HTRA1 (P = 4.2e-20).
Conclusions:
The study highlights a clear association between the ARMS2-HTRA1 locus and higher RPD load. Although the CFH locus association did not achieve genome-wide significance, a suggestive link was observed. Three novel associations unique to RPD were identified, albeit for uncommon genetic variants. Further studies with larger sample sizes are needed to explore these findings.
More Related Videos
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
11:35Screening for Functional Non-coding Genetic Variants Using Electrophoretic Mobility Shift Assay EMSA and DNA-affinity Precipitation Assay DAPA
Published on: August 21, 2016
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
02:46Genetic Screens
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
01:05Single Nucleotide Polymorphisms-SNPs
01:33Pleiotropy