A case-control collapsing analysis identifies retinal dystrophy genes associated with ophthalmic disease in patients with no pathogenic ABCA4 variants.

ABSTRACT:

Purpose

Variants in the ABCA4 gene are causal for a variety of retinal dystrophy phenotypes, including Stargardt disease (STGD1). However, 15% of patients who present with symptoms compatible with STGD1/ABCA4 disease do not have identifiable causal ABCA4 variants. We hypothesized that a case-control collapsing analysis in ABCA4-negative patients with compatible symptoms would provide an objective measure to identify additional disease genes.

Methods

We performed a genome-wide enrichment analysis of "qualifying variants"-ultrarare variants predicted to impact protein function-in protein-coding genes in 79 unrelated cases and 9028 unrelated controls.

Results

Despite modest sample size, two known retinal dystrophy genes, PRPH2 and CRX, achieved study-wide significance (p

SUBMITTER: Wolock CJ 

PROVIDER: S-EPMC6768764 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature