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

L. J. Kopplin, R. P. Igo, Y. Wang, T. A. Sivakumaran, S. A. Hagstrom, N. S. Peachey, P. J. Francis, M. L. Klein, J. P. Sangiovanni, E. Y. Chew, G. J.T. Pauer, G. M. Sturgill, T. Joshi, L. Tian, Q. Xi, A. K. Henning, K. E. Lee, R. Klein, B. E.K. Klein, S. K. Iyengar

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


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 × 10-64) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10 -60) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P5.3 × 10-15), 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 × 10-4), 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.

Original languageEnglish (US)
Pages (from-to)609-621
Number of pages13
JournalGenes and Immunity
Issue number8
StatePublished - Dec 2010
Externally publishedYes


  • association testing
  • macular degeneration
  • melanosome trafficking

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)


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