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Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility.

Publication ,  Journal Article
Chintalapudi, SR; Maria, D; Di Wang, X; Bailey, JNC; NEIGHBORHOOD consortium; International Glaucoma Genetics consortium; Hysi, PG; Wiggs, JL ...
Published in: Nat Commun
November 24, 2017

Glaucoma is a multi-factorial blinding disease in which genetic factors play an important role. Elevated intraocular pressure is a highly heritable risk factor for primary open angle glaucoma and currently the only target for glaucoma therapy. Our study helps to better understand underlying genetic and molecular mechanisms that regulate intraocular pressure, and identifies a new candidate gene, Cacna2d1, that modulates intraocular pressure and a promising therapeutic, pregabalin, which binds to CACNA2D1 protein and lowers intraocular pressure significantly. Because our study utilizes a genetically diverse population of mice with known sequence variants, we are able to determine that the intraocular pressure-lowering effect of pregabalin is dependent on the Cacna2d1 haplotype. Using human genome-wide association study (GWAS) data, evidence for association of a CACNA2D1 single-nucleotide polymorphism and primary open angle glaucoma is found. Importantly, these results demonstrate that our systems genetics approach represents an efficient method to identify genetic variation that can guide the selection of therapeutic targets.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 24, 2017

Volume

8

Issue

1

Start / End Page

1755

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Chintalapudi, S. R., Maria, D., Di Wang, X., Bailey, J. N. C., NEIGHBORHOOD consortium, International Glaucoma Genetics consortium, … Jablonski, M. M. (2017). Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Nat Commun, 8(1), 1755. https://doi.org/10.1038/s41467-017-00837-5
Chintalapudi, Sumana R., Doaa Maria, Xiang Di Wang, Jessica N Cooke Bailey, NEIGHBORHOOD consortium, International Glaucoma Genetics consortium, Pirro G. Hysi, Janey L. Wiggs, Robert W. Williams, and Monica M. Jablonski. “Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility.Nat Commun 8, no. 1 (November 24, 2017): 1755. https://doi.org/10.1038/s41467-017-00837-5.
Chintalapudi SR, Maria D, Di Wang X, Bailey JNC, NEIGHBORHOOD consortium, International Glaucoma Genetics consortium, et al. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Nat Commun. 2017 Nov 24;8(1):1755.
Chintalapudi, Sumana R., et al. “Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility.Nat Commun, vol. 8, no. 1, Nov. 2017, p. 1755. Pubmed, doi:10.1038/s41467-017-00837-5.
Chintalapudi SR, Maria D, Di Wang X, Bailey JNC, NEIGHBORHOOD consortium, International Glaucoma Genetics consortium, Hysi PG, Wiggs JL, Williams RW, Jablonski MM. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Nat Commun. 2017 Nov 24;8(1):1755.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 24, 2017

Volume

8

Issue

1

Start / End Page

1755

Location

England

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease