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Copy number variation at chromosome 5q21.2 is associated with intraocular pressure.

Publication ,  Journal Article
Nag, A; Venturini, C; Hysi, PG; Arno, M; Aldecoa-Otalora Astarloa, E; Macgregor, S; Hewitt, AW; Young, TL; Mitchell, P; Viswanathan, AC ...
Published in: Invest Ophthalmol Vis Sci
May 1, 2013

PURPOSE: Glaucoma is a major cause of blindness in the world. Recent genome-wide association studies (GWAS) have identified common genetic variants for glaucoma, but still a significant heritability gap remains. We hypothesized that copy number variants (CNVs) might influence part of the susceptibility to glaucoma or its related quantitative endophenotypes. METHODS: THIS STUDY EXAMINED THE ASSOCIATION BETWEEN CNVS AND INTRAOCULAR PRESSURE (IOP), THE MAJOR MODIFIABLE RISK FACTOR FOR PRIMARY OPEN-ANGLE GLAUCOMA (POAG), IN THREE POPULATION PANELS OF EUROPEAN ANCESTRY: the TwinsUK cohort (n = 1047), the Australian Twin Eye Study (n = 561), and the Wellcome Trust Case-Control Consortium 2 (WTCCC2)/Blue Mountains Eye Study (BMES) (n = 1660). We also used PCR-based assays to investigate a locus of interest that we found associated with IOP in a POAG case-control panel of European ancestry from London, United Kingdom. RESULTS: WE IDENTIFIED ASSOCIATIONS BETWEEN IOP AND TWO CNV REGIONS IN THE TWINSUK COHORT: 5q21.2 (P = 0.003) overlapping the gene RAB9BP1 and 12p13.3 (P = 0.03) overlapping the genes SLC2A14 and SLC2A3. The Australian Twin Eye Study and BMES both replicated the 5q21.2 CNV association and direction of effect (P = 0.001 and P = 0.02, respectively). A meta-analysis across all the cohorts showed that presence of a copy number change at this locus increased IOP by 1.56 mm Hg (P = 1.24 × 10(-6)). In the case-control study, the 5q21.2 CNV locus did not show association with high-pressure (≥21 mm Hg) POAG cases. CONCLUSIONS: The 5q21.2 CNV locus could represent a novel locus controlling IOP. Interestingly, this IOP locus is located in close vicinity to the previously widely replicated GLC1G linkage locus for glaucoma, for which subsequent studies have not reached consensus on the causal gene.

Duke Scholars

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

May 1, 2013

Volume

54

Issue

5

Start / End Page

3607 / 3612

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Ophthalmology & Optometry
  • Middle Aged
  • Medical Staff, Hospital
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma
 

Citation

APA
Chicago
ICMJE
MLA
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Nag, A., Venturini, C., Hysi, P. G., Arno, M., Aldecoa-Otalora Astarloa, E., Macgregor, S., … Hammond, C. J. (2013). Copy number variation at chromosome 5q21.2 is associated with intraocular pressure. Invest Ophthalmol Vis Sci, 54(5), 3607–3612. https://doi.org/10.1167/iovs.13-11952
Nag, Abhishek, Cristina Venturini, Pirro G. Hysi, Matthew Arno, Estibaliz Aldecoa-Otalora Astarloa, Stuart Macgregor, Alex W. Hewitt, et al. “Copy number variation at chromosome 5q21.2 is associated with intraocular pressure.Invest Ophthalmol Vis Sci 54, no. 5 (May 1, 2013): 3607–12. https://doi.org/10.1167/iovs.13-11952.
Nag A, Venturini C, Hysi PG, Arno M, Aldecoa-Otalora Astarloa E, Macgregor S, et al. Copy number variation at chromosome 5q21.2 is associated with intraocular pressure. Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3607–12.
Nag, Abhishek, et al. “Copy number variation at chromosome 5q21.2 is associated with intraocular pressure.Invest Ophthalmol Vis Sci, vol. 54, no. 5, May 2013, pp. 3607–12. Pubmed, doi:10.1167/iovs.13-11952.
Nag A, Venturini C, Hysi PG, Arno M, Aldecoa-Otalora Astarloa E, Macgregor S, Hewitt AW, Young TL, Mitchell P, Viswanathan AC, Mackey DA, Hammond CJ. Copy number variation at chromosome 5q21.2 is associated with intraocular pressure. Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3607–3612.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

May 1, 2013

Volume

54

Issue

5

Start / End Page

3607 / 3612

Location

United States

Related Subject Headings

  • Young Adult
  • White People
  • Risk Factors
  • Ophthalmology & Optometry
  • Middle Aged
  • Medical Staff, Hospital
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma