An international collaborative family-based whole-genome linkage scan for high-grade myopia.
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.
Li
Yi-Ju
YJ
Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA. yiju.li@duke.edu
Guggenheim
Jeremy A
JA
Bulusu
Anuradha
A
Metlapally
Ravikanth
R
Abbott
Diana
D
Malecaze
Francois
F
Calvas
Patrick
P
Rosenberg
Thomas
T
Paget
Sandrine
S
Creer
Rosalind C
RC
Kirov
George
G
Owen
Michael J
MJ
Zhao
Bei
B
White
Tristan
T
Mackey
David A
DA
Young
Terri L
TL