title: Applying genetics in inflammatory disease drug discovery.
abstract: Recent groundbreaking work in genetics has identified thousands of small-effect genetic variants throughout the genome that are associated with almost all major diseases. These genome-wide association studies (GWAS) are often proposed as a source of future medical breakthroughs. However, with several notable exceptions, the journey from a small-effect genetic variant to a functional drug has proven arduous, and few examples of actual contributions to drug discovery exist. Here, we discuss novel approaches of overcoming this hurdle by using instead public genetics resources as a pragmatic guide alongside existing drug discovery methods. Our aim is to evaluate human genetic confidence as a rationale for drug target selection.
authors.affiliation: Department of PharmacoGenetics, Novo Nordisk, Novo Nordisk Park, Måløv, Denmark; Department of Integrative Systems Biology, Center for Biological Sequence Analysis, DTU, Lyngby, Denmark. Electronic address: lassefolkersen@gmail.com.
authors.forename: Lasse
authors.initials: L
authors.lastname: Folkersen
authors.affiliation: Department of Molecular Immunology, Novo Nordisk, Seattle, WA, USA.
authors.forename: Shameek
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of PharmacoGenetics, Novo Nordisk, Novo Nordisk Park, Måløv, Denmark.
authors.forename: Klaus Stensgaard
authors.initials: KS
authors.lastname: Frederiksen
authors.affiliation: Department of PharmacoGenetics, Novo Nordisk, Novo Nordisk Park, Måløv, Denmark.
authors.forename: Pernille
authors.initials: P
authors.lastname: Keller
authors.affiliation: Department of Molecular Immunology, Novo Nordisk, Seattle, WA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Fox
authors.affiliation: Department of PharmacoGenetics, Novo Nordisk, Novo Nordisk Park, Måløv, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics; D058990:Molecular Targeted Therapy
chemical_list: D000893:Anti-Inflammatory Agents