title: Genome-wide analyses identify common variants associated with macular telangiectasia type 2.
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.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Thomas S
authors.identifier: http://orcid.org/0000-0003-0992-4042
authors.initials: TS
authors.lastname: Scerri
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Quaglieri
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cai
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Zernant
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Nori
authors.initials: N
authors.lastname: Matsunami
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Baird
authors.affiliation: The Lowy Medical Research Institute, La Jolla, California, USA.
authors.forename: Lea
authors.initials: L
authors.lastname: Scheppke
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonelli
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.|Vitreous Retina Macula Consultants of New York, New York, New York, USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Yannuzzi
authors.affiliation: The Lowy Medical Research Institute, La Jolla, California, USA.|Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Friedlander
authors.affiliation: Medical Retina Department, Moorfields Eye Hospital NHS Foundation Trust, London, UK.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Egan
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, UK.
authors.forename: Marcus
authors.initials: M
authors.lastname: Fruttiger
authors.affiliation: Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Leppert
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.|Department of Pathology and Cell Biology, Columbia University, New York, New York, USA.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.|Department of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Melanie
authors.identifier: http://orcid.org/0000-0001-5132-0774
authors.initials: M
authors.lastname: Bahlo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D058456:Retinal Telangiectasis / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult