Baird, Paul N.

Cantsilieris, Stuart

Grassmann, Felix

Guymer, Robyn H.

Hewitt, Alex W.

Richardson, Andrea J.

Schmied, Denise

Schulz-Kuhnt, Anja Sabrina

Vote, Brendan J.

Weber, Bernhard H.F.

White, Stefan J.

Journal of Neuroinflammation

English

PubMed

Felix Grassmann

Stuart Cantsilieris

Anja-Sabrina Schulz-Kuhnt

Stefan J. White

Andrea J Richardson

Alex W Hewitt

Brendan J. Vote

Denise Schmied

Robyn H Guymer

Bernhard H.F. Weber

Paul N. Baird

Springer - Publisher Connector

Multiallelic copy number variation in the complement component 4A (C4A) gene is associated with late-stage age-related macular degeneration (AMD)

Background: Age-related macular degeneration (AMD) is the leading cause of vision loss in Western societies with a strong genetic component. Candidate gene studies as well as genome-wide association studies strongly implicated genetic variations in complement genes to be involved in disease risk. So far, no association of AMD with complement component 4 (C4) was reported probably due to the complex nature of the C4 locus on chromosome 6. Methods: We used multiplex ligation-dependent probe amplification (MLPA) to determine the copy number of the C4 gene as well as of both relevant isoforms, C4A and C4B, and assessed their association with AMD using logistic regression models. Results: Here, we report on the analysis of 2645 individuals (1536 probands and 1109 unaffected controls), across three different centers, for multiallelic copy number variation (CNV) at the C4 locus. We find strong statistical significance for association of increased copy number of C4A (OR 0.81 (0.73; 0.89); P = 4.4 x 10(-5)), with the effect most pronounced in individuals over 78 years (OR 0.67 (0.55; 0.81)) and females (OR 0.77 (0.68; 0.87)). Furthermore, this association is independent of known AMD-associated risk variants in the nearby CFB/C2 locus, particularly in females and in individuals over 78 years. Conclusions: Our data strengthen the notion that complement dysregulation plays a crucial role in AMD etiology, an important finding for early intervention strategies and future therapeutics. In addition, for the first time, we provide evidence that multiallelic CNVs are associated with AMD pathology

Weber, Bernhard H. F.

Schulz-Kuhnt, Anja-Sabrina

University of Regensburg Publication Server

Research Archive

https://epub.uni-regensburg.de/34168/1/art%253A10.1186%252Fs12974-016-0548-0.pdf

Multiallelic copy number variation in the complement component 4A (C4A) gene is associated with late-stage age-related macular degeneration (AMD)

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

University of Regensburg Publication Server

Research Archive