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- Study Description
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Important Links and Information
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- Instructions for requestors
- Data Use Certification (DUC) Agreement
- Talking Glossary of Genetic Terms
Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. To further our understanding of AMD genetics, we examined the contribution of common and rare genetic variation in the International AMD Genomics Consortium that included ~50,000 samples of 26 AMD case - control cohorts that were jointly genotyped. Analyzing 16,144 patients with late stage AMD and 17,832 controls, we identified 52 independently associated common and rare variants distributed across 34 loci. Besides these single variant signals, we also observed gene-based enrichment of very rare coding variants (frequency < 0.1%) in cases that implicated causal roles for CFH, CFI and TIMP3 in three of the known AMD risk loci. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.
- Study Weblinks:
- Study Design:
- Case-Control
- Study Type:
- Case-Control
- dbGaP estimated ancestry using GRAF-pop
- Total number of consented subjects: 35358
- Subject Sample Telemetry Report (SSTR)
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- Authorized Access
- Publicly Available Data
- Link to other NCBI resources related to this study
- Study Inclusion/Exclusion Criteria
Inclusion criteria:
Cases: Avanced AMD cases with GA and/or CNV in at least one eye and age at first diagnosis >= 50 years, intermediate AMD cases with pigmentary changes in the RPE or more than five macular drusen greater than 63μm and age at first diagnosis >= 50 years.
Controls: Without known advanced or intermediate AMD.
Recruitment and ascertainment strategies varied by study.
Exclusion criteria (cases and controls):
- Duplicated and related individuals (kinship coefficient Φ >= 0.0884, i.e. 3rd degree relatives or closer)
- Subjects with discrepancies between reported gender and sex chromosomal information or with atypical sex chromosome configurations
- Subjects with genotyping call rates < 98.5%
- Molecular Data
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Type Source Platform Number of Oligos/SNPs SNP Batch Id Comment Targeted Genotyping Illumina HumanCoreExome - Goncalo 15038949 N/A N/A Custom Array: Includes customized content. Imputation 1000 Genomes Project 1000 Genomes N/A N/A Phase I, version 3, SHAPEIT2 Reference - Selected Publications
- Diseases/Traits Related to Study (MeSH terms)
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- Primary Phenotype: Macular Degeneration
- Geographic Atrophy
- Wet Macular Degeneration
- Links to Related Genes
- Authorized Data Access Requests
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See articles in PMC citing this study accession
- Study Attribution
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Principal Investigator
- Margaret M. DeAngelis, PhD. John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, School of Medicine, Salt Lake City, UT, USA.
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Principal Investigator (on NEI genotyping grant)
- Gonçalo Abecasis, D.Phil. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
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Genetic Statistician
- Lars Fritsche, PhD. Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
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Funding Source
- CIDR Program contract number: HHSN268201200008I. National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
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Genotyping Center
- Center for Inherited Disease Research (CIDR). Johns Hopkins University, Baltimore, MD, USA.
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Principal Investigator