An International Collaborative Family-Based Whole-Genome Linkage Scan for High-Grade Myopia

Abstract

Purpose 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 ≥ 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 1343-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.

Genetic Variations in the Dopamine System and Facial Expression Recognition in Healthy Chinese College Students

“…In addition, 3 genetic markers ( DRD4 _VNTR, MAOA _VNTR, and COMT rs4680) were ascertained by the standard PCR procedures [22][23][24] . The GenCall scores of the loci in the current study ranged from 0.45 to 0.95; this is above the conventional cutoff point of 0.25 for inclusion [25] . The GenCall score (ranging from 0 to 1, the higher the better) is a quality measure for each genotype in the Illumina system that indicates how close a genotype is to the center of the cluster of other samples assigned to the same genotypes [26] .…”

Replication Study SupportsCTNND2as a Susceptibility Gene for High Myopia

“…27 This locus was further supported by an additional genome-wide linkage scan of Asian families. 37 Recently, a GWAS study on Singapore Chinese revealed that genetic variations in the noncoding region of CTNND2, the SNPs rs6885224 and rs12716080, were associated with high myopia. 33 The CTNND2 gene is located inside the linkage interval of MYP16.…”

A decade in search of myopia genes

“…However, it is unclear from this data whether this locus is distinct from MYP13. The results of the first large-scale study of high-grade myopia (254 families from 5 independent sites, 1411 subjects) tentatively confirmed the Xq28 locus although the peak LOD score was only 1.6.9, and these results appeared to only be confined to the Duke subset (Duke University Medical Center, Durham, NC, USA) using the DOM model (40). A much higher although non-significant LOD score of 2.4.0 was obtained for the MYP13 locus (Xq24), which again suggests confirmation, but was confined to the Cardiff (Wales) subset.…”

“…Li et al also identified a 9.9.7 cM region in the MYP3 locus (12q21) using the SNP approach rather than microsatellite analysis (40). Total HLOD scores for this region were 3.4.8 with strongest contributions from the Duke subset.…”