Quantitative trait linkage analysis of ocular refraction in four populations
by Wojciechowski, Robert, Ph.D., THE JOHNS HOPKINS UNIVERSITY, 2008, 233 pages; 3288555

Abstract:

Purpose. Refractive development is influenced by a host of environmental and genetic factors. Genetic studies have identified several loci putatively linked to refraction phenotypes, few of which have been reproduced in independent samples. We performed quantitative trait locus (QTL) linkage analyses in four populations to discover genomic regions responsible for mediating ocular refraction. We also performed genome-wide linkage meta-analyses in these populations to identify regions that may be linked to ocular refraction across populations.

Methods. We recruited 242 extended families to participate in the Myopia Family Study including: 49 Ashkenazi Jewish (ASHK), 96 African American (AFRAM), 36 White/Caucasian (CAUC) and 61 Old Order Amish. A total of 1,308 individuals were genotyped with polymorphic microsatellite markers. Multipoint genomewide QTL linkage analyses were performed separately for each population using the extended regression-based method implemented in the program Merlin-regress. Empirical significance levels were determined via whole-genome gene-dropping simulations. Linkage meta-analyses were performed by combining P-values across populations at 2cM intervals and within 10 and 20cM bins. Meta-analysis P-values were obtained empirically.

Results. Two regions met genomewide (GW) significance criteria for linkage to ocular refraction: 1p36 in the ASHK (LOD=8.9, GW P<0.01) and 7p15 in the AFRAM (LOD=5.87, GW P=0.026) families. Suggestive evidence of linkage was found at 12824 (LOD=4.583, GW P=0.13) in the CAUC sample, and at 5qter (LOD=3.271, GW P=0.38) in the OOA. In addition to the population-specific linkage peaks, the meta-analysis revealed suggestive evidence of linkage to a region on chr. 4g21-22 (pointwise P=0.00214).

Conclusions. We identified several regions that may harbor genes that mediate ocular refraction in human populations. Our results also suggest considerable locus heterogeneity in the genetic etiology of ocular refraction, indicating that several, possibly interacting, genes likely play a role in refractive development.

 
AdvisersJoan E. Bailey-Wilson; Terri Beaty
SchoolTHE JOHNS HOPKINS UNIVERSITY
SourceDAI/B 68-11, p. , Feb 2008
Source TypeDissertation
SubjectsGenetics; Ophthalmology; Epidemiology
Publication Number3288555
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