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Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.

Publication ,  Journal Article
Bailey, JNC; Loomis, SJ; Kang, JH; Allingham, RR; Gharahkhani, P; Khor, CC; Burdon, KP; Aschard, H; Chasman, DI; Igo, RP; Hysi, PG; Brown, AA ...
Published in: Nat Genet
February 2016
Published version (DOI) Link to item

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Duke Scholars

Allison Elizabeth Ashley-Koch
Author Allison Elizabeth Ashley-Koch Medicine, Nephrology
Tien Yin Wong
Author Tien Yin Wong Ophthalmology
Michael Arthur Hauser
Author Michael Arthur Hauser Medicine, Medical Genetics
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Published In

Nat Genet

DOI

10.1038/ng.3482

EISSN

1546-1718

Publication Date

February 2016

Volume

48

Issue

2

Start / End Page

189 / 194

Location

United States

Related Subject Headings

  • Thioredoxin Reductase 2
  • Polymorphism, Single Nucleotide
  • Humans
  • Glaucoma, Open-Angle
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Forkhead Transcription Factors
  • Developmental Biology
  • Ataxin-2
  • 3105 Genetics
 

Citation

APA
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ICMJE
MLA
NLM
Bailey, J. N. C., Loomis, S. J., Kang, J. H., Allingham, R. R., Gharahkhani, P., Khor, C. C., … Wiggs, J. L. (2016). Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet, 48(2), 189–194. https://doi.org/10.1038/ng.3482
Bailey, Jessica N Cooke, Stephanie J. Loomis, Jae H. Kang, R Rand Allingham, Puya Gharahkhani, Chiea Chuen Khor, Kathryn P. Burdon, et al. “Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.” Nat Genet 48, no. 2 (February 2016): 189–94. https://doi.org/10.1038/ng.3482.
Bailey JNC, Loomis SJ, Kang JH, Allingham RR, Gharahkhani P, Khor CC, et al. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet. 2016 Feb;48(2):189–94.
Bailey, Jessica N. Cooke, et al. “Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma.” Nat Genet, vol. 48, no. 2, Feb. 2016, pp. 189–94. Pubmed, doi:10.1038/ng.3482.
Bailey JNC, Loomis SJ, Kang JH, Allingham RR, Gharahkhani P, Khor CC, Burdon KP, Aschard H, Chasman DI, Igo RP, Hysi PG, Glastonbury CA, Ashley-Koch A, Brilliant M, Brown AA, Budenz DL, Buil A, Cheng C-Y, Choi H, Christen WG, Curhan G, De Vivo I, Fingert JH, Foster PJ, Fuchs C, Gaasterland D, Gaasterland T, Hewitt AW, Hu F, Hunter DJ, Khawaja AP, Lee RK, Li Z, Lichter PR, Mackey DA, McGuffin P, Mitchell P, Moroi SE, Perera SA, Pepper KW, Qi Q, Realini T, Richards JE, Ridker PM, Rimm E, Ritch R, Ritchie M, Schuman JS, Scott WK, Singh K, Sit AJ, Song YE, Tamimi RM, Topouzis F, Viswanathan AC, Verma SS, Vollrath D, Wang JJ, Weisschuh N, Wissinger B, Wollstein G, Wong TY, Yaspan BL, Zack DJ, Zhang K, Study E-NE, ANZRAG Consortium, Weinreb RN, Pericak-Vance MA, Small K, Hammond CJ, Aung T, Liu Y, Vithana EN, MacGregor S, Craig JE, Kraft P, Howell G, Hauser MA, Pasquale LR, Haines JL, Wiggs JL. Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. Nat Genet. 2016 Feb;48(2):189–194.

Published In

Nat Genet

DOI

10.1038/ng.3482

EISSN

1546-1718

Publication Date

February 2016

Volume

48

Issue

2

Start / End Page

189 / 194

Location

United States

Related Subject Headings

  • Thioredoxin Reductase 2
  • Polymorphism, Single Nucleotide
  • Humans
  • Glaucoma, Open-Angle
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Forkhead Transcription Factors
  • Developmental Biology
  • Ataxin-2
  • 3105 Genetics