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The complement system is the first line of defense against foreign intruders, and deregulation of this system has been described in multiple diseases. In age-related macular degeneration (AMD), patients have higher complement activation levels compared to controls. Recently, a combination of three single nucleotide polymorphisms (SNPs) in genes of the complement system, referred to as a complotype, has been described to increase complement activation  in vitro . Here we describe a novel complotype composed of  CFB  (rs4151667)- CFB  (rs641153)- CFH  (rs800292), which is strongly associated with both AMD disease status (p = 5.84*10 −13 ) and complement activation levels  in vivo  (p = 8.31*10 −9 ). The most frequent genotype combination of this complotype was associated with the highest complement activation levels in both patients and controls. These findings are relevant in the context of complement-lowering treatments for AMD that are currently under development. Patients with a genetic predisposition to higher complement activation levels will potentially benefit the most of such treatments.

A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo