Genome-wide association identifies ATOH7 as a major gene determining human optic disc size

Macgregor, Stuart, Hewitt, Alex W., Hysi, Pirro G., Ruddle, Jonathan B., Medland, Sarah E., Henders, Anjali K., Gordon, Scott D., Andrew, Toby, McEvoy, Brian, Sanfilippo, Paul G., Carbonaro, Francis, Tah, Vikas, Li, Yi Ju, Bennett, Sonya L., Craig, Jamie E., Montgomery, Grant W., Tran-Viet, Khanh-Nhat, Brown, Nadean L., Spector, Timothy D., Martin, Nicholas G., Young, Terri L., Hammond, Christopher J. and Mackey, David A. (2010) Genome-wide association identifies ATOH7 as a major gene determining human optic disc size. Human Molecular Genetics, 19 13: 2716-2724. doi:10.1093/hmg/ddq144

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Author Macgregor, Stuart
Hewitt, Alex W.
Hysi, Pirro G.
Ruddle, Jonathan B.
Medland, Sarah E.
Henders, Anjali K.
Gordon, Scott D.
Andrew, Toby
McEvoy, Brian
Sanfilippo, Paul G.
Carbonaro, Francis
Tah, Vikas
Li, Yi Ju
Bennett, Sonya L.
Craig, Jamie E.
Montgomery, Grant W.
Tran-Viet, Khanh-Nhat
Brown, Nadean L.
Spector, Timothy D.
Martin, Nicholas G.
Young, Terri L.
Hammond, Christopher J.
Mackey, David A.
Title Genome-wide association identifies ATOH7 as a major gene determining human optic disc size
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2010-07-01
Sub-type Article (original research)
DOI 10.1093/hmg/ddq144
Volume 19
Issue 13
Start page 2716
End page 2724
Total pages 9
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Optic nerve assessment is important formany blinding diseases,with cup-to-disc ratio (CDR) assessments commonly  used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, weperformed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P 5 6.2 3 10-10, near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a metaanalysis of the combined data yielding P 5 3.4 3 10-10. Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P 5 1.3 3 10-10 to 4.3 3 10-11, top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P 5 1.5 3 10-7, in the gene RFTN1. Direct sequencing ofATOH7 in 12 patients withoptic nerve hypoplasia, one of the leadingcauses ofblindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher’s exact P 5 0.0136). Furthermore, the Arg65Gly variantwas found to have very low frequency (0.00066) in an additional set of 672 controls.

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Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Created: Wed, 30 Mar 2011, 17:02:29 EST by Debbie Banks on behalf of School of Medicine