Investigating the modulation of genetic effects on late AMD by age and sex: Lessons learned and two additional loci

• DOI: 10.1371/journal.pone.0194321
• Publication Date: 2018-03-12T17:41:59Z
• Authors: Thomas W. Winkler; Caroline Brandl; Felix Grassmann; Mathias Gorski; Klaus Stark; Julika Loss; Bernhard H. F. Weber; Iris M. Heid
• Keywords: Genome-wide Association Study; Clusterin

Late-stage age-related macular degeneration (AMD) is the leading cause of visual impairment in elderly with a complex etiology. The most important non-modifiable risk factors for onset and progression late AMD are age genetic factors, however, little known about interplay between genetics or sex. Here, we conducted large-scale age- sex-stratified genome-wide association study (GWAS) using 1000 Genomes imputed ExomeChip data (>12 million variants). were established by International Age-related Macular Degeneration Genomics Consortium (IAMDGC) from 16,144 cases 17,832 controls. Our systematic search interaction effects yielded significantly stronger among younger individuals at two loci (near CFH ARMS2/HTRA1). Accounting gene-age joint test identified additional compared to previous main effect scan. One these novel GWAS locus, near retinal clusterin-like protein (CLUL1) gene, other, retinaldehyde binding 1 (RLBP1), was recently analysis nuclear mitochondrial variants. Despite considerable power our data, neither sex-dependent nor opposite directions older observed. This first incorporate age, sex their AMD. Results diminish potential role etiology yet highlight importance existence age-dependent effects.