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Making Biological Sense of Genetic Studies of Age-Related Macular Degeneration

Singh, Nivedita, Swaroop, Anand, Ratnapriya, Rinki·2021·Advances in Experimental Medicine and Biology
DOI 10.1007/978-3-030-66014-7_8
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Abstract

Age-related macular degeneration (AMD) is a major cause of blindness in older individuals worldwide. The disease is characterized by deposition of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, RPE atrophy and death of photoreceptors. AMD is a complex disease with multiple genetic and non-genetic risk factors. Genome-wide association studies (GWAS) have identified 52 variants at 34 genetic loci associated with AMD. A majority of the AMD-GWAS variants are present in non-coding region of the genome and could quantitatively impact distinct human traits [called quantitative trait loci (QTLs)] by affecting regulation of gene expression. The integration of different regulatory features, such as open-chromatin regions, histone marks, transcription factor binding sites, with AMD-GWAS can provide meaningful insights into variant's function. However, functional interpretation of variant-gene relationship in AMD is challenging because of inadequate understanding of cell-type specific and context-dependent information in disease-relevant tissues. Here we focus on the role of sequencing-based omic studies in assigning biological meaning to disease-associated variants and genes. We also discuss the methods and model systems that can be utilized to unravel molecular mechanisms of a complex disorder like AMD.

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Metadata

Authors
Singh, N., Swaroop, A., & Ratnapriya, R.
Affiliations
National Institutes of Health (US)
Corresponding author
Swaroop, Anand
ORCID
Venue
Advances in Experimental Medicine and Biology
Publisher
Springer International Publishing
Published
2021
Volume
1256
Pages
201-219
ISSN
  • 0065-2598 (ISSN-L)
  • 2214-8019
DOI
10.1007/978-3-030-66014-7_8
OpenAlex
W3155324975
Cited by
11
References
102
Citations by year
2026: 1 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 1
FWCI
13.55
Type
book chapter
Language
en
Open access
closed
Licence
Locations
  • Advances in experimental medicine and biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
Keywords
age-related macular degeneration, genetic loci, non-coding variants, quantitative trait loci, gene expression regulation, open chromatin, histone modifications, transcription factor binding sites, retinal pigment epithelium, drusen, photoreceptor atrophy, cell type-specific gene regulation, model systems, molecular mechanisms
MeSH terms
Aged, Humans, Macular Degeneration, Retina, Bruch Membrane, Genome-Wide Association Study, Retinal Pigment Epithelium

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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