Dataset Information

Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10???) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10???) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 × 10?¹?), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10??), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.

SUBMITTER: Kopplin LJ

PROVIDER: S-EPMC3375062 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.

Kopplin L J LJ Igo R P RP Wang Y Y Sivakumaran T A TA Hagstrom S A SA Peachey N S NS Francis P J PJ Klein M L ML SanGiovanni J P JP Chew E Y EY Pauer G J T GJ Sturgill G M GM Joshi T T Tian L L Xi Q Q Henning A K AK Lee K E KE Klein R R Klein B E K BE Iyengar S K SK

Genes and immunity 20100923 8

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement fa ...[more]

PMID: 20861866

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Project description:PurposeTo determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls.MethodsMetabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.ResultsOf the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.ConclusionsThese data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.

Dataset Information

Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.

Publications

Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.

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