Genome-wide scan for myopia in the Old Order Amish.
OBJECTIVE
To identify myopia susceptibility genes influencing common myopia in 34 Old Order Amish families, a genetically well-defined founder population.


METHODS
A prospective study of families with myopia consisting of a minimum of two individuals affected with myopia.


METHODS
Extended families consisting of at least two siblings affected with myopia were ascertained. A genome-wide linkage scan using 387 markers was conducted by the Center for Inherited Disease Research (CIDR). Linkage analyses were conducted with parametric (autosomal dominant, fixed penetrance model) and nonparametric methods. Model-free linkage analysis was also performed maximizing over penetrance and over dominance (that is, fitting a wide range of both dominant and recessive models).


RESULTS
Under the fixed penetrance model, the maximum two-point heterogeneity LOD score (HLOD) was 1.59 at D20S451 and the maximum multipoint HLOD was 1.92 at D6S1021. The nonparametric maximum multipoint (NPL) at D3S2427 had a P-value of .0005. Under the model-free analysis, multipoint heterogeneity LOD scores of 2.03 were observed on both chromosomes 8 (under a recessive model between D8S1130 and D8S1106) and X (under a recessive model between DXS6800 and DXS6789). Reanalyses of chromosomes 3, 6, 8, 20, and X using the best penetrance models resulted in maximum multipoint HLODs of 1.84 at D3S3053; 1.84 at D3S2427; 2.04 at D8S1130; and 2.34 at DXS6800.


CONCLUSIONS
The locus on chromosome 8p23 independently confirms a report by Hammond and associates mapping a myopia quantitative trait loci (QTL) to this region.
Stambolian
Dwight
D
Department of Ophthalmology, Stellar Chance Laboratories Rm. 313, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104, USA. stamboli@mail.med.upenn.edu
Ciner
Elise B
EB
Reider
Lauren C
LC
Moy
Chris
C
Dana
Debra
D
Owens
Robert
R
Schlifka
Melissa
M
Holmes
Taura
T
Ibay
Grace
G
Bailey-Wilson
Joan E
JE
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human; D023281:Genomics; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D009216:Myopia / Q000235:genetics*; D010375:Pedigree; D011446:Prospective Studies; D040641:Quantitative Trait Loci