Evidence map›Paper›PMID 32246154›Full record

ArticleHuman molecular genetics2020

Family-based exome sequencing identifies rare coding variants in age-related macular degeneration.

Rinki Ratnapriya, İlhan E Acar, Maartje J Geerlings, Kari Branham, Alan Kwong, Nicole T M Saksens, Marc Pauper, Jordi Corominas, Madeline Kwicklis, David Zipprer and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
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  7. Genetic variants associated with age-related episodic memory decline implicate distinct memory pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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  18. Frontiers in genetics · 2022
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 2 countries.

Rinki RatnapriyaNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
İlhan E AcarDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Maartje J GeerlingsDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Kari BranhamDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Alan KwongCenter for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Nicole T M SaksensDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Marc PauperDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Jordi CorominasDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Madeline KwicklisNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
David ZipprerNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
Margaret R StarostikNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
Mohammad OthmanDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Beverly YasharDepartment of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Goncalo R AbecasisCenter for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA.
Emily Y ChewNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
Deborah A FerringtonDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.
Carel B HoyngDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Anand SwaroopNeurobiology, Neurodegeneration and Repair Laboratory (NNRL), National Eye Institute, Bethesda, MD 20892, USA.
Anneke I den HollanderDepartment of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen 6500, The Netherlands.
Radboud University Medical Center · NLNational Eye Institute · USUniversity of Michigan–Ann Arbor · USBaylor College of Medicine · USRadboud University Nijmegen · NLUniversity of Minnesota · US

Funding

Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
Regulation of gene expression in the retinaZ01EY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2008 to 2008
$2.4M
Intramural NIH HHS Z01 EY000450
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) have identified 52 independent variants at 34 genetic loci that are associated with age-related macular degeneration (AMD), the most common cause of incurable vision loss in the elderly worldwide. However, causal genes at the majority of these loci remain unknown. In this study, we performed whole exome sequencing of 264 individuals from 63 multiplex families with AMD and analyzed the data for rare protein-altering variants in candidate target genes at AMD-associated loci. Rare coding variants were identified in the CFH, PUS7, RXFP2, PHF12 and TACC2 genes in three or more families. In addition, we detected rare coding variants in the C9, SPEF2 and BCAR1 genes, which were previously suggested as likely causative genes at respective AMD susceptibility loci. Identification of rare variants in the CFH and C9 genes in our study validated previous reports of rare variants in complement pathway genes in AMD. We then extended our exome-wide analysis and identified rare protein-altering variants in 13 genes outside the AMD-GWAS loci in three or more families. Two of these genes, SCN10A and KIR2DL4, are of interest because variants in these genes also showed association with AMD in case-control cohorts, albeit not at the level of genome-wide significance. Our study presents the first large-scale, exome-wide analysis of rare variants in AMD. Further independent replications and molecular investigation of candidate target genes, reported here, would assist in gaining novel insights into mechanisms underlying AMD pathogenesis.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyAgedAged, 80 and overExomeExome SequencingHumansMacular DegenerationMaleMiddle AgedNAV1.8 Voltage-Gated Sodium ChannelPolymorphism, Single NucleotideReceptors, KIR2DL4KIR2DL4 protein, humanNAV1.8 Voltage-Gated Sodium ChannelReceptors, KIR2DL4SCN10A protein, human

Identifiers

PMID32246154
PMCPMC7390936
OpenAlexW3014860370

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.