June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Pleiotropic effect of genetic variants associated with complex diseases and traits in age-related macular degeneration
Author Affiliations & Notes
  • Felix Grassmann
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • Christina Kiel
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • Mathias Gorski
    Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Klaus Stark
    Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Martina Zimmermann
    Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Iris M Heid
    Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany
  • Bernhard HF Weber
    Institute of Human Genetics, University of Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships   Felix Grassmann, None; Christina Kiel, None; Mathias Gorski, None; Klaus Stark, None; Martina Zimmermann, None; Iris Heid, None; Bernhard Weber, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2983. doi:
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      Felix Grassmann, Christina Kiel, Mathias Gorski, Klaus Stark, Martina Zimmermann, Iris M Heid, Bernhard HF Weber; Pleiotropic effect of genetic variants associated with complex diseases and traits in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2983.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of vision loss in western societies and is caused by both environmental and genetic risk factors. With regard to the latter, several associated risk loci harbor genes involved in the complement system, high density lipoprotein metabolism or extracellular matrix homeostasis. These pathways are known for their pleiotropic role in other conditions, such as cardiovascular disease, auto-immune diseases and cancer. Here, we aimed to investigate the extend of overlap between the genetic risk of various complex diseases and traits and the genetic risk for AMD.

Methods : First, we catalogued 2,331 previously published, genome-wide significant variations associated with 82 complex diseases or traits. Next, we computed a genetic score by calculating the sum of risk increasing alleles for each disease or trait. Consequently, a higher genetic score indicates that an individual has more risk/trait increasing alleles of a given disease or trait. For each score, we computed the association with late stage AMD using a dataset provided by the International AMD Genomics consortium (IAMDGC) including 16,144 late stage AMD cases and 17,832 controls. We also assessed the association of each variation individually with late stage AMD risk in order to identify novel disease loci with strong evidence for pleiotropy.

Results : Nineteen genetic scores of complex diseases and traits were significantly associated with AMD risk (FDR < 0.01). Most notably, all genetic scores related to autoimmunity were elevated in AMD patients (P < 5.85x10-09), while scores related to cardiovascular disease were reduced in AMD patients compared to controls (P < 3.10x10-05). We also found that the genetic scores of melanoma and related malignancies were higher in AMD patients (P < 8.43x10-05). In addition, 32 out of 2,331 variants, which were used to compute the genetic scores, were significantly associated with AMD (FDR < 0.01), implicating 25 novel, pleiotropic loci in AMD risk.

Conclusions : Our findings demonstrate a substantial overlap between the genetic risk of complex diseases/traits and the genetic risk for AMD and provide evidence for 25 novel, pleiotropic loci associated with AMD. Our findings highlight common disease pathways that may facilitate to develop multi-use drug targets.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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