title: An international collaborative family-based whole-genome linkage scan for high-grade myopia.
abstract: OBJECTIVE
  Several nonsyndromic high-grade myopia loci have been mapped primarily by microsatellite markers and a limited number of pedigrees. In this study, whole-genome linkage scans were performed for high-grade myopia, using single nucleotide polymorphisms (SNPs) in 254 families from five independent sites.
  
  
  METHODS
  Genomic DNA samples from 1411 subjects were genotyped (Linkage Panel IVb; Illumina, San Diego, CA). Linkage analyses were performed on 1201 samples from 10 Asian, 12 African-American, and 221 Caucasian families, screening for 5744 SNPs after quality-control exclusions. Two disease states defined by sphere (SPH) and spherical equivalence (SE; sphere+cylinder/2) were analyzed. Parametric and nonparametric two-point and multipoint linkage analyses were performed using the FASTLINK, HOMOG, and MERLIN programs. Multiple stratified datasets were examined, including overall, center-specific, and race-specific. Linkage regions were declared suggestive if they had a peak LOD score >or= 1.5.
  
  
  RESULTS
  The MYP1, MYP3, MYP6, MYP11, MYP12, and MYP14 loci were replicated. The novel region q34.11 on chromosome 9 (max NPL= 2.07 at rs913275) was identified. Chromosome 12, region q21.2-24.12 (36.59 cM, MYP3 locus) showed significant linkage (peak HLOD = 3.48) at rs337663 in the overall dataset by SPH and was detected by the Duke, Asian, and Caucasian subsets as well. Potential shared interval was race dependent-a 9.4-cM region (rs163016-rs1520724) driven by the Asian subset and a 13.43-cM region (rs163016-rs1520724) driven by the Caucasian subset.
  
  
  CONCLUSIONS
  The present study is the largest linkage scan to date for familial high-grade myopia. The outcomes will facilitate the identification of genes implicated in myopic refractive error development and ocular growth.
authors.affiliation: Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. yiju.li@duke.edu
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: Anuradha
authors.initials: A
authors.lastname: Bulusu
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Metlapally
authors.forename: Diana
authors.initials: D
authors.lastname: Abbott
authors.forename: Francois
authors.initials: F
authors.lastname: Malecaze
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
authors.forename: Sandrine
authors.initials: S
authors.lastname: Paget
authors.forename: Rosalind C
authors.initials: RC
authors.lastname: Creer
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Bei
authors.initials: B
authors.lastname: Zhao
authors.forename: Tristan
authors.initials: T
authors.lastname: White
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young