Ordered subset analysis supports a glaucoma locus at GLC1I on chromosome 15 in families with earlier adult age at diagnosis

Abigail Woodroffe, Charles M. Krafchak, Nobuo Fuse, Paul R. Lichter, Sayoko E. Moroi, Robert Schertzer, Catherine A. Downs, William L. Duren, Michael Boehnke, Julia E. Richards

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Open angle glaucoma (OAG) is a complex disorder with varying etiologies due to multiple genes and environmental effects. This genetic heterogeneity can confound efforts to map loci. Increased homogeneity in a sample can be achieved using either ordered subset analysis (OSA) which groups families, or individual OSA (IOSA), which groups individuals based on disease related covariates. Recently, GLC1I was mapped to 15q11-13 in families with early adult onset of OAG. We tested for linkage to GLC1I in an independent sample of 167 individuals in 25 multiplex OAG families of European descent. We carried out nonparametric linkage analysis on the complete set of 25 families and obtained a maximum LOD score of 1.00 at 9.0 cM. Using mean age at diagnosis (AAD) across the affected individuals within each family to order the families as a proxy for age at onset, we found a maximum OSA LOD score of 2.09 (p=0.021) at 26.1 cM. The mean (±s.d.) AAD across the 14 earlier AAD families that contributed to the OSA LOD score was 50.6 years (±5.38); the mean AAD for the other 1210 later AAD families that did not contribute to the OSA LOD score (the high-AAD) was 61.7 years (±3.50). We also ran IOSA on our families using AAD as our covariate on which to subset affected individuals. The maximum LOD score was 1.01 at 14.3 cM when ordering subjects from early to late AAD. Ordered subset analysis of this sample has provided evidence of linkage close to the previously identified GLC1I glaucoma locus on 15q11-13 in families with middle-aged mean age at diagnosis.

Original languageEnglish
Pages (from-to)1068-1074
Number of pages7
JournalExperimental Eye Research
Volume82
Issue number6 SPEC. ISS.
DOIs
Publication statusPublished - 2006 Jun

Keywords

  • age at diagnosis
  • complex traits
  • genetic heterogeneity
  • juvenile glaucoma
  • linkage mapping
  • normal tension glaucoma
  • open-angle glaucoma
  • ordered subset analysis

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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