Genetic disruption of serine biosynthesis is a key driver of macular telangiectasia type 2 aetiology and progression.

ABSTRACT:

Background

Macular telangiectasia type 2 (MacTel) is a rare, heritable and largely untreatable retinal disorder, often comorbid with diabetes. Genetic risk loci subtend retinal vascular calibre and glycine/serine/threonine metabolism genes. Serine deficiency may contribute to MacTel via neurotoxic deoxysphingolipid production; however, an independent vascular contribution is also suspected. Here, we use statistical genetics to dissect the causal mechanisms underpinning this complex disease.

Methods

We integrated genetic markers for MacTel, vascular and metabolic traits, and applied Mendelian randomisation and conditional and interaction genome-wide association analyses to discover the causal contributors to both disease and spatial retinal imaging sub-phenotypes.

Results<

SUBMITTER: Bonelli R 

PROVIDER: S-EPMC7945323 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature