Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in age-related macular degeneration (AMD)

This article reports a well‐powered age‐related macular degeneration (AMD) case–control association study in the HMCN1 gene, showing that common variants do not account for a substantial proportion of AMD cases. Thus, the consistent linkage peak observed by several genome‐wide linkage scans within the 1q32 region is unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition, the analysis provides comprehensive data suggesting that low‐frequency variants encoding possible functional amino acid polymorphisms in the HMCN1 gene may not contribute substantially to disease, although HMCN1 mutations may still confer disease susceptibility in a small subset of patients. Interestingly, the HMCN1 p.Gln5346Arg mutation, which is thought to be a causal mutation in a large AMD pedigree segregating the disease as a single‐gene trait, appears to occur in our control cohort as a low‐frequency polymorphism with an allele frequency of approximately 0.0026. Hum Mutat 28(4), 406–413, 2007. © 2007 Wiley‐Liss, Inc.