title: An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error.
abstract: OBJECTIVE
  To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites.
  
  
  METHODS
  Genomic DNA samples from 254 families were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel IVb. Quantitative trait linkage analysis was performed on 225 Caucasian families and 4,656 markers after accounting for linkage disequilibrium and quality control exclusions. Two refractive quantitative phenotypes, sphere (SPH) and spherical equivalent (SE), were analyzed. The SOLAR program was used to estimate identity by descent probabilities and to conduct two-point and multipoint quantitative trait linkage analyses.
  
  
  RESULTS
  We found 29 markers and 11 linkage regions reaching peak two-point and multipoint logarithms of the odds (LODs)>1.5. Four linkage regions revealed at least one LOD score greater than 2: chromosome 6q13-6q16.1 (LOD=1.96 for SPH, 2.18 for SE), chromosome 5q35.1-35.2 (LOD=2.05 for SPH, 1.80 for SE), chromosome 7q11.23-7q21.2 (LOD=1.19 for SPH, 2.03 for SE), and chromosome 3q29 (LOD=1.07 for SPH, 2.05 for SE). Among these, the chromosome 6 and chromosome 5 regions showed the most consistent results between SPH and SEM. Four linkage regions with multipoint scores above 1.5 are near or within the known myopia (MYP) loci of MYP3, MYP12, MYP14, and MYP16. Overall, we observed consistent linkage signals across the SPH and SEM phenotypes, although scores were generally higher for the SEM phenotype.
  
  
  CONCLUSIONS
  Our quantitative trait linkage analyses of a large myopia family cohort provided additional evidence for several known MYP loci, and identified two additional potential loci at chromosome 6q13-16.1 and chromosome 5q35.1-35.2 for myopia. These results will benefit the efforts toward determining genes for myopic refractive error.
authors.affiliation: Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Abbott
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Guggenheim
authors.forename: Ravikanth
authors.initials: R
authors.lastname: Metlapally
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: Tetyana
authors.initials: T
authors.lastname: Zayats
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Sheng
authors.initials: S
authors.lastname: Feng
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D000328:Adult; D001315:Australia; D015415:Biomarkers / Q000378:metabolism*; D002877:Chromosomes, Human / Q000235:genetics; D015331:Cohort Studies; D005060:Europe; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007391:International Cooperation; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012030:Refractive Errors / Q000235:genetics*; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers