Evidence map›Paper›PMID 37934784›Full record

ArticleHuman molecular genetics2024

Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration.

Alan Kwong, Matthew Zawistowski, Lars G Fritsche, Xiaowei Zhan, Jennifer Bragg-Gresham, Kari E Branham, Jayshree Advani, Mohammad Othman, Rinki Ratnapriya, Tanya M Teslovich and 4 more

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

Article in Human molecular genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
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

14 authors at 7 institutions in 1 country.

Alan KwongDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States.
Matthew ZawistowskiDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States.
Lars G FritscheDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States.
Xiaowei ZhanSouthwestern Medical Center, University of Texas, 5323 Harry Hines Blvd, Dallas, TX 75390, United States.
Jennifer Bragg-GreshamKidney Epidemiology and Cost Center, Department of Internal Medicine-Nephrology, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States.
Kari E BranhamDepartment of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105, United States.
Jayshree AdvaniNeurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, 6 Center Drive, MSC 0610, Bethesda, MD 20892, United States.
Mohammad OthmanDepartment of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, 1000 Wall St, Ann Arbor, MI 48105, United States.
Rinki RatnapriyaNeurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, 6 Center Drive, MSC 0610, Bethesda, MD 20892, United States.
Tanya M TeslovichRegeneron Pharmaceuticals Inc., 777 Old Saw Mill River Rd, Tarrytown, NY 10591, United States.
Dwight StambolianDepartment of Ophthalmology, Perelman School of Medicine, University of Pennsylvania Medical School, 51 N. 39th Street, Philadelphia, PA 19104, United States.
Emily Y ChewDivision of Epidemiology and Clinical Application, National Eye Institute, National Institutes of Health, 10 Center Drive Building 10-CRC, Bethesda, MD 20892, United States.
Gonçalo R AbecasisDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States.
Anand SwaroopNeurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, 6 Center Drive, MSC 0610, Bethesda, MD 20892, United States.
University of Michigan–Ann Arbor · USNational Eye Institute · USStatistical Research (United States) · USNational Institutes of Health · USRegeneron (United States) · USThe University of Texas Southwestern Medical Center · USUniversity of Pennsylvania · US

Funding

Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
Deconstructing and Modeling the Single Cell Architecture of the Age-Related Macular Degeneration Retina and RPE/ChoroidR01EY031209 · NEI · UNIVERSITY OF PENNSYLVANIA · PI DEANGELIS, MARGARET M, LI, MINGYAO · 2020 to 2024
$2.7M
Age-Related Eye Disease Follow-up Study (AREDS) Follow-up StudyZIAEY000489 · NEI · NATIONAL EYE INSTITUTE · PI CHEW, EMILY Y · 2009 to 2025
$639k
Intramural NIH HHS ZIA EY000489Intramural NIH HHS ZIA EY000546NEI NIH HHS R01 EY031209NEI NIH HHS ZIAEY000546
6 · The paper itself

Abstract

Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, the genetic contribution to complex traits is still largely difficult to interpret. We report a genome-wide association study of 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million genetic variants. Our study reveals significant single-variant association signals at four loci and independent gene-based signals in CFH, C2, C3, and NRTN. Using data from the Exome Aggregation Consortium (ExAC) for a gene-based test, we demonstrate an enrichment of predicted rare loss-of-function variants in CFH, CFI, and an as-yet unreported gene in AMD, ORMDL2. Our method of using a large variant list without individual-level genotypes as an external reference provides a flexible and convenient approach to leverage the publicly available variant datasets to augment the search for rare variant associations, which can explain additional disease risk in AMD.

Indexed as

Genome-Wide Association StudyMacular DegenerationComplement Factor HGenetic Predisposition to DiseaseGenetic TestingGenotypeHumansPolymorphism, Single NucleotideWhole Genome SequencingComplement Factor Haginggenetic variationgenome-wide association studymacular degenerationvision losswhole genome sequencing

Identifiers

PMID37934784
PMCPMC10840384
OpenAlexW4388451148

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.