Journal article

Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder

Roberto Bonelli, Victoria E Jackson, Aravind Prasad, Jacob E Munro, Tjebo FC Heeren, Nikolas Pontikos, Lea Scheppke, Martin Friedlander, Catherine E Egan, Rando Allikmets, Brendan RE Ansell, Melanie Bahlo

Cold Spring Harbor Laboratory


Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed a genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel genome-wide significant loci (p<5E-8), and confirmed all three previously reported loci. Using MAGMA, eQTL and transcriptome-wide association analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, and retinal vasculature and thickness. Mendelian randomization indicated a likely causative role of serine (FDR=3.9E-47) and glycine depletion (FDR=0.006) as well as alanine abundance (FDR=0.009). Polygenic risk scoring achieve..

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