Genetic Dissection of Myopia: Evidence for Linkage of Ocular Axial Length to Chromosome 5q
Received 10 April 2007; received in revised form 7 August 2007; accepted 9 August 2007. published online 26 October 2007.
Purpose
To estimate heritability and locate quantitative trait loci influencing axial length.
Design
Classic twin study of monozygotic and dizygotic twins reared together.
Participants
Eight hundred ninety-three individuals from 460 families were recruited through the Twin Eye Study in Tasmania and the Brisbane Adolescent Twin Study (BATS) and had ocular axial length measured.
Methods
Structural equation modeling on the entire sample was used to estimate genetic and environmental components of variation in axial length. Analysis of existing microsatellite marker genomewide linkage scan data was performed on 318 individuals from 142 BATS families.
Main Outcome Measure
Ocular axial length.
Results
The heritability estimate for axial length, adjusted for age and sex, in the full sample was 0.81. The highest multipoint logarithm of the odds (LOD) score observed was 3.40 (genomewide P = 0.0004), on chromosome 5q (at 98 centimorgans [cM]). Additional regions with suggestive multipoint LOD scores were also identified on chromosome 6 (LOD scores, 2.13 at 76 cM and 2.05 at 83 cM), chromosome 10 (LOD score, 2.03 at 131 cM), and chromosome 14 (LOD score, 2.84 at 97 cM).
Conclusion
Axial length, a major endophenotype for refractive error, is highly heritable and is likely to be influenced by one or more genes on the long arm of chromosome 5.
Available online: October 26, 2007.
1Genetic Epidemiology Unit, Queensland Institute of Medical Research, Brisbane, Australia.
2Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
3National Health and Medical Research Council Centre for Clinical Eye Research, Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia.
4Ophthalmology Department, Royal Hospital for Sick Children, Glasgow, United Kingdom.
5Twin Research and Genetic Epidemiology Unit, St. Thomas' Hospital, London, United Kingdom.
6Department of Ophthalmology, Royal Hobart Hospital, University of Tasmania, Hobart, Australia.
Correspondence to Assoc Prof D. A. Mackey, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, Victoria, Australia 3002.
Manuscript no. 2007-489.
Collection of phenotypes and DNA samples was supported by grants from the Queensland Cancer Fund, Fortitude Valley, Australia; Australian National Health and Medical Research Council (NHMRC), Canberra, Australia (nos. 950998, 981339, 241944 [NGM]; 350415 [DAM, JEC, CJH]); National Cancer Institute, Bethesda, Maryland (no. CA88363 [NGM, GWM]); Ophthalmic Research Institute of Australia, Surry Hills, Australia; American Health Assistance Foundation, Clarksburg, Maryland; and Jack Brockhoff Foundation, Doncaster East, Australia. The genome scans were supported by the Australian NHMRC's Program in Medical Genomics (grant no. NHMRC-219178 [NGM, GWM]) and Center for Inherited Disease Research at Johns Hopkins University, Baltimore, Maryland (NGM). The latter is fully funded through a federal contract from the National Institutes of Health, Bethesda, Maryland, to Johns Hopkins University (contract no. N01-HG-65403). The Australian Twin Registry is supported by an NHMRC Enabling Grant (no. 310667). Dr Mackey is the recipient of a Pfizer Australia (West Ryde, Australia) research fellowship.
No author has any other commercial or competing interests related to the research.
ABSTRACT