Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder
- Author(s)
- Bonelli, R; Jackson, VE; Prasad, A; Munro, JE; Farashi, S; Heeren, TFC; Pontikos, N; Scheppke, L; Friedlander, M; Egan, CA; Allikmets, R; Ansell, BRE; Bahlo, M;
- Details
- Publication Year 2021-03-02,Volume 4,Issue #1,Page 274
- Journal Title
- Communications Biology
- Abstract
- 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 < 5 × 10(-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 = 3.9 × 10(-)(47)) and glycine depletion (FDR = 0.006) as well as alanine abundance (FDR = 0.009). Polygenic risk scoring achieved an accuracy of 0.74 and was associated in UKBiobank with retinal damage (p = 0.009). This represents the largest genetic study on MacTel to date and further highlights genetically-induced systemic and tissue-specific metabolic dysregulation in MacTel patients, which impinges on retinal health.
- Publisher
- NPG
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 33654266
- Publisher's Version
- https://doi.org/10.1038/s42003-021-01788-w
- Open Access at Publisher's Site
https://doi.org/10.1038/s42003-021-01788-w- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2021-05-13 09:20:16
Last Modified: 2021-05-13 09:22:59