Inferring Human Phenotype Networks from Genome-Wide Genetic Associations

  • Christian Darabos
  • Kinjal Desai
  • Richard Cowper-Sal·lari
  • Mario Giacobini
  • Britney E. Graham
  • Mathieu Lupien
  • Jason H. Moore
Part of the Lecture Notes in Computer Science book series (LNCS, volume 7833)


Networks are commonly used to represent and analyze large and complex systems of interacting elements. We build a human phenotype network (HPN) of over 600 physical attributes, diseases, and behavioral traits; based on more than 6,000 genetic variants (SNPs) from Genome-Wide Association Studies data. Using phenotype-to-SNP associations, and HapMap project data, we link traits based on the common patterns of human genetic variations, expanding previous studies from a gene-centric approach to that of shared risk-variants. The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. Additional network metrics hint that the HPN shares properties with social networks. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present a collection of documented clinical connections supported by the network. Furthermore, we highlight phenotypes modules and links that may underlie yet undiscovered genetic interactions. Despite its simplicity and current limitations the HPN shows tremendous potential to become a useful tool both in the unveiling of the diseases’ common biology, and in the elaboration of diagnosis and treatments.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Christian Darabos
    • 1
  • Kinjal Desai
    • 1
  • Richard Cowper-Sal·lari
    • 1
  • Mario Giacobini
    • 2
  • Britney E. Graham
    • 1
  • Mathieu Lupien
    • 3
  • Jason H. Moore
    • 1
  1. 1.Department of GeneticsThe Geisel Medical School at Dartmouth CollegeLebanonU.S.A.
  2. 2.Computational Epidemiology Group, Department of Veterinary Sciences, and Complex Systems Unit, Molecular Biotechnology CenterUniversity of TorinoItaly
  3. 3.Ontario Cancer Institute, Princess Margaret Cancer Center-University Health Network, Ontario Institute for Cancer Research and the Department of Medical BiophysicsUniversity of TorontoTorontoCanada

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