title: Early adult-onset POAG linked to 15q11-13 using ordered subset analysis.
abstract: OBJECTIVE
  Primary open-angle glaucoma (POAG) is a complex inherited disorder. It has been demonstrated in other complex disorders that phenotypic heterogeneity may be the result of genetic heterogeneity and that stratification analysis can be used to increase the power of detection. Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity.
  
  
  METHODS
  Eighty-six multiplex families with POAG were clinically ascertained for genetic analysis. Age at diagnosis (AAD) was used as a surrogate for age of onset in affected family members. Nine genetic markers within the 15q11-13 interval on chromosome 15 were used for OSA analysis.
  
  
  RESULTS
  An 11-cM linkage interval with a peak LOD score of 3.24 centered at the GABRB3 locus (P = 0.013 by permutation test) was identified in a subset of 15 families, which represents 17% of the total dataset (15/86 families). The mean AAD for the affected OSA families was 44.1 +/- 9.1 years (SD). The mean AAD for the complementary group was 61.3 +/- 10.4 years. African-American and white families were well represented in the OSA subset.
  
  
  CONCLUSIONS
  Linkage was identified for POAG to an 11-cM region on chromosome 15, designated GLC1I. This result provides further evidence that AAD and other phenotypic traits can be used as stratification variables to identify genes in complex disorders such as POAG and suggests that the 15q11-13 locus is one of the largest genetic contributors to POAG identified to date.
authors.affiliation: Duke University Eye Center and the Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA. allin002@mc.duke.edu
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hauser
authors.forename: Karen R
authors.initials: KR
authors.lastname: Larocque-Abramson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Santiago-Turla
authors.forename: Bob
authors.initials: B
authors.lastname: Broomer
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Del Bono
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Graham
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008126:Lod Score; D008297:Male; D008875:Middle Aged
chemical_list: D005819:Genetic Markers