title: Disease-specific target selection: a critical first step down the right road.
abstract: Relevance of a drug target for a disease is often inferred with strong belief but fragile evidence. Here, a program for early identification of human disease-specific drug targets using high-throughput genetic associations is described. Large numbers of well-characterized patients (>1000) and matched controls are screened for genetic associations using several thousand (>7000) single nucleotide polymorphisms from more than 1500 genes. The genes were selected because they are members of target classes for which there are precedents for high-throughput chemical screening technology. This review summarizes the methods and intensive data analyses leading to target gene identification for type 2 diabetes mellitus, including the statistical permutation methodology used to correct for many variables.
authors.affiliation: GlaxoSmithKline R&D, Research Triangle Park, NC 27709, USA. allen.d.roses@gsk.com
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Burns
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chissoe
authors.forename: Lefkos
authors.initials: L
authors.lastname: Middleton
authors.forename: Pamela
authors.initials: P
authors.lastname: St Jean
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics; D015195:Drug Design; D023281:Genomics / Q000379:methods*; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D013223:Statistics as Topic; D013678:Technology, Pharmaceutical / Q000379:methods*