| Title: | Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder |
| Journal: | Communications Biology |
| Published: | 2 Mar 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33654266/ |
| DOI: | https://doi.org/10.1038/s42003-021-01788-w |
| URL: | https://www.nature.com/articles/s42003-021-01788-w.pdf |
| Citations: | 32 (15 in last 2 years) as of 8 Aug 2024 |
Publication 9564
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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.</p>
13 Authors
- Roberto Bonelli
- Victoria E. Jackson
- Aravind Prasad
- Jacob E. Munro
- Samaneh Farashi
- Tjebo F. C. Heeren
- Nikolas Pontikos
- Lea Scheppke
- Martin Friedlander
- Catherine A. Egan
- Rando Allikmets
- Brendan R. E. Ansell
- Melanie Bahlo
1 Application
| Application ID | Title |
|---|---|
| 36610 | Exploring the genetic basis of healthy development and ageing: gene discovery and methods development. |
Enabling scientific discoveries that improve human health