Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Thomas S Scerri; Anna Quaglieri; Carolyn Cai; Jana Zernant; Nori Matsunami; Lisa Baird; Lea Scheppke; Roberto Bonelli; Lawrence A Yannuzzi; Martin Friedlander; MacTel Project Consortium; Catherine A Egan; Marcus Fruttiger; Mark Leppert; Rando Allikmets; Melanie Bahlo

doi:10.1038/ng.3799

Genome-wide analyses identify common variants associated with macular telangiectasia type 2

Nat Genet. 2017 Apr;49(4):559-567. doi: 10.1038/ng.3799. Epub 2017 Feb 27.

Authors

Thomas S Scerri^{1

2}, Anna Quaglieri^{1

2}, Carolyn Cai³, Jana Zernant³, Nori Matsunami⁴, Lisa Baird⁴, Lea Scheppke⁵, Roberto Bonelli^{1

2}, Lawrence A Yannuzzi^{3

6}, Martin Friedlander^{5

7}; MacTel Project Consortium; Catherine A Egan⁸, Marcus Fruttiger⁹, Mark Leppert⁴, Rando Allikmets^{3

10}, Melanie Bahlo^{1

2

11}

Affiliations

¹ The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
² Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
³ Department of Ophthalmology, Columbia University, New York, New York, USA.
⁴ Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
⁵ The Lowy Medical Research Institute, La Jolla, California, USA.
⁶ Vitreous Retina Macula Consultants of New York, New York, New York, USA.
⁷ Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
⁸ Medical Retina Department, Moorfields Eye Hospital NHS Foundation Trust, London, UK.
⁹ UCL Institute of Ophthalmology, University College London, London, UK.
¹⁰ Department of Pathology and Cell Biology, Columbia University, New York, New York, USA.
¹¹ Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia.

PMID: 28250457
DOI: 10.1038/ng.3799

Abstract

Idiopathic juxtafoveal retinal telangiectasis type 2 (macular telangiectasia type 2; MacTel) is a rare neurovascular degenerative retinal disease. To identify genetic susceptibility loci for MacTel, we performed a genome-wide association study (GWAS) with 476 cases and 1,733 controls of European ancestry. Genome-wide significant associations (P < 5 × 10^-8) were identified at three independent loci (rs73171800 at 5q14.3, P = 7.74 × 10^-17; rs715 at 2q34, P = 9.97 × 10^-14; rs477992 at 1p12, P = 2.60 × 10^-12) and then replicated (P < 0.01) in an independent cohort of 172 cases and 1,134 controls. The 5q14.3 locus is known to associate with variation in retinal vascular diameter, and the 2q34 and 1p12 loci have been implicated in the glycine/serine metabolic pathway. We subsequently found significant differences in blood serum levels of glycine (P = 4.04 × 10^-6) and serine (P = 2.48 × 10^-4) between MacTel cases and controls.

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Child
Child, Preschool
Female
Genetic Loci / genetics
Genetic Predisposition to Disease / genetics*
Genome-Wide Association Study / methods
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Retinal Telangiectasis / genetics*
White People / genetics
Young Adult

Supplementary concepts

Idiopathic Juxtafoveal Retinal Telangiectasia

Grants and funding

R01 EY013435/EY/NEI NIH HHS/United States