Recombinant haplotypes narrow the ARMS2/HTRA1 association signal for age-related macular degeneration

International AMD Genomics Consortium (IAMDGC)

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 10 × 10-773 and 6.7 × 10-5. This now allows prioritization of the gene of interest for subsequent functional studies.

Original languageEnglish
Pages (from-to)919-924
Number of pages6
JournalGenetics
Volume205
Issue number2
DOIs
StatePublished - Feb 2017

Keywords

  • ARMS2/HTRA1 gene locus
  • Age-related macular degeneration
  • Genetic association studies
  • Haplotypes
  • Linkage disequilibrium

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