Journal article

Recombinant Haplotypes Narrow the ARMS2/HTRA1 Association Signal for Age-Related Macular Degeneration

Felix Grassmann, Iris M Heid, Bernhard HF Weber



Age-related macular degeneration (AMD) is the leading cause of blindness in ageing societies, triggered by both environmental and genetic factors. The strongest genetic signal for AMD with odds ratios of up to 2.8 per adverse allele was found previously over a chromosomal region in 10q26 harboring two genes, ARMS2 and HTRA1, although with little knowledge as to which gene or genetic variation is functionally relevant to AMD pathology. In this study, we analyzed rare recombinant haplotypes in 16,144 AMD cases and 17,832 controls from the International AMD Genomics Consortium and identified variants in ARMS2 but not HTRA1 to exclusively carry the AMD risk with P-values between 1.0 × 10-773 and..

View full abstract


Awarded by German Federal Ministry of Education and Research

Awarded by German Research Foundation

Funding Acknowledgements

The authors thank Paul N. Baird (Ocular Genetics Unit, Centre for Eye Research, Australia) for critically reading the manuscript. The work was funded in part by grants from the German Federal Ministry of Education and Research (BMBF 01ER1206 and 01ER1507) to I.M.H., by the institutional budget for Research and Teaching from the Freestate of Bavaria and the German Research Foundation (WE 1259/19-2) to BHFW.