Abstract

Importance: ), which is associated with lower circulating CFI protein levels, but the nature of the relationship is unclear. Objective: Can genetic factors be used to infer whether low circulating CFI is associated with AAMD risk? Design: Two-sample inverse variance weighted Mendelian Randomisation (MR) was used to evaluate evidence for a relationship between CFI levels and AAMD risk, comparing CFI levels from genetically predefined subsets in AAMD and control cohorts. Setting: Published genetic and proteomic data was combined with data from cohorts of Geographic Atrophy (GA) patients in a series of MR analyses. Participants: We derived genetic instruments for systemic CFI level in 3,301 healthy European participants in the INTERVAL study. To evaluate a genetic causal odds ratio (OR) for the effect of CFI levels on AAMD risk, we used results from a genome-wide association study of 12,711 AAMD cases and 14,590 European controls from the International AMD Genomics Consortium (IAMDGC), and CFI levels from patients entered into the research studies SCOPE and SIGHT. Results: ). Conclusion and relevance: Excellent concordance in direction and effect size derived from rare and common variant calculations provide good genetic evidence for a potentially causal role of lower CFI level increasing AAMD risk.

Authors	Jones, Amy V; MacGregor, Stuart; Han, Xikun; Francis, James; Harris, Claire; , ; Kavanagh, David; Lotery, Andrew; Waheed, Nadia
Journal	Ophthalmology science
Pages
Volume	2
Date	1/01/2022
Grant ID
Funding Body
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.xops.2022.100146