Evidence map›Paper›PMID 22705344›Full record

SynthesisOphthalmology2012

Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.

Lucia Sobrin, Stephan Ripke, Yi Yu, Jesen Fagerness, Tushar R Bhangale, Perciliz L Tan, Eric H Souied, Gabriëlle H S Buitendijk, Joanna E Merriam, Andrea J Richardson and 24 more

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PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Ophthalmology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 3 pooled it
9.9field-weighted citation impact, top 1% 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

44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 87 citations in OpenAlex.

  1. Pooled it
  2. ABCA1 rs1883025 polymorphism and risk of age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2016
    Pooled it
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  9. Article
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  11. The hypothetical molecular mechanism of the ethnic variations in the manifestation of age-related macular degeneration; focuses on the functions of the most significant susceptibility genes.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2024
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Investigational Agents in Development for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2021
    Review
  17. Article
  18. 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

34 authors at 17 institutions in 6 countries.

Lucia SobrinDepartment of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Stephan Ripke
Yi Yu
Jesen Fagerness
Tushar R Bhangale
Perciliz L Tan
Eric H Souied
Gabriëlle H S Buitendijk
Joanna E Merriam
Andrea J Richardson
Soumya Raychaudhuri
Robyn Reynolds
Kimberly A Chin
Aaron Y Lee
Nicolas Leveziel
Donald J Zack
Peter Campochiaro
R Theodore Smith
Gaetano R Barile
Ruth E Hogg
Usha Chakravarthy
Timothy W Behrens
André G Uitterlinden
Cornelia M van Duijn
Johannes R Vingerling
Milam A Brantley
Paul N Baird
Caroline C W Klaver
Rando Allikmets
Nicholas Katsanis
Robert R Graham
John P A Ioannidis
Mark J Daly
Johanna M Seddon
Columbia University · USErasmus MC · NLHarvard University · USDuke University · USGenentechQueen's University Belfast · GBTufts Medical Center · USTufts University · USUniversité Paris-Est Créteil · FRUniversity of Melbourne · AUBrigham and Women's Hospital · USErasmus University Rotterdam · NLInstitut de la Vision · FRJohns Hopkins University · USUniversity of Ioannina · GRVanderbilt University · USWashington University in St. Louis · US

Funding

COORDINATING CENTER FOR AMD PREVENTION TRIALU10EY012279 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MAGUIRE, MAUREEN G · 1999 to 2006
$14.9M
Development of Complement Modulating Therapeutics for AMDR24EY017404 · NEI · UNIVERSITY OF UTAH · PI HAGEMAN, GREGORY S · 2006 to 2010
$14.8M
Mass Eye and Ear-Vision Clinical Scientist Development ProgramK12EY016335 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Reza Dana · 2004 to 2026
$12.3M
ETIOLOGIC STUDIES OF AGE-RELATED MACULAR DEGENERATIONR01EY011309 · NEI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SEDDON, JOHANNA M · 2003 to 2017
$9.3M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059571 · NIMH · UNIVERSITY OF CHICAGO · PI GEJMAN, PABLO V. · 1999 to 2007
$8.0M
Genetic Variation in Age-Related Macular DegenerationR01EY013435 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALLIKMETS, RANDO L · 2001 to 2014
$7.7M
A Genome-Wide Association Study of SchizophreniaU01MH079469 · NIMH · NORTHSHORE UNIVERSITY HEALTHSYSTEM · PI GEJMAN, PABLO V. · 2007 to 2009
$4.4M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH060879 · NIMH · WASHINGTON UNIVERSITY · PI CLONINGER, C. ROBERT · 1999 to 2006
$2.7M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059586 · NIMH · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SILVERMAN, JEREMY M. · 1999 to 2006
$1.9M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH061675 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI LEVINSON, DOUGLAS FREDERICK · 1999 to 2007
$1.8M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059587 · NIMH · EMORY UNIVERSITY · PI AMIN, FAROOQ · 1999 to 2006
$1.8M
MOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059565 · NIMH · UNIVERSITY OF COLORADO DENVER · PI FREEDMAN, ROBERT · 1999 to 2006
$1.7M
NEI NIH HHS EY012211NEI NIH HHS EY012261NEI NIH HHS EY012279NEI NIH HHS K12 EY016335NEI NIH HHS K12-EY16335NEI NIH HHS R01 EY011309NEI NIH HHS R01 EY013435NEI NIH HHS R01-EY11309NEI NIH HHS R01-EY13435NEI NIH HHS R24 EY017404NEI NIH HHS R24-EY017404NIMH NIH HHS R01 MH059565NIMH NIH HHS R01 MH059566NIMH NIH HHS R01 MH059571NIMH NIH HHS R01 MH059586NIMH NIH HHS R01 MH059587NIMH NIH HHS R01 MH059588NIMH NIH HHS R01 MH060870NIMH NIH HHS R01 MH060879NIMH NIH HHS R01 MH061675NIMH NIH HHS R01 MH067257NIMH NIH HHS R01 MH081800NIMH NIH HHS R01 MH59565NIMH NIH HHS R01 MH59566NIMH NIH HHS R01 MH59571NIMH NIH HHS R01 MH59586NIMH NIH HHS R01 MH59587NIMH NIH HHS R01 MH59588NIMH NIH HHS R01 MH60870NIMH NIH HHS R01 MH60879NIMH NIH HHS R01 MH61675NIMH NIH HHS R01 MH67257NIMH NIH HHS R01 MH81800NIMH NIH HHS U01 MH046276NIMH NIH HHS U01 MH046318NIMH NIH HHS U01 MH079469NIMH NIH HHS U01 MH079470NIMH NIH HHS U01 MH46289NIMH NIH HHS U01 MH79469NIMH NIH HHS U01 MH79470
6 · The paper itself

Abstract

purposeTo investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes.

designSibling correlation study and genome-wide association study (GWAS).

participantsFor the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls.

methodsParticipants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts.

main outcome measuresConcordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes.

resultsThe difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 × 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 × 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 × 10(-14) for combined discovery and replication analysis).

conclusionsWhether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies.

Indexed as

Polymorphism, Single NucleotideChoroidal NeovascularizationFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGenotypeGeographic AtrophyHigh-Temperature Requirement A Serine Peptidase 1HumansMacular DegenerationMaleProteinsRisk FactorsSerine EndopeptidasesSiblingsARMS2 protein, humanHigh-Temperature Requirement A Serine Peptidase 1HTRA1 protein, humanProteinsSerine Endopeptidases

Identifiers

PMID22705344
PMCPMC3899891
OpenAlexW2050523881

What OpenQuestion holds

Textmetadata
LicenceTDM
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.