The ANKS1B gene and its associated phenotypes: focus on CNS drug response

Pharmacogenomics. 2019 Jun;20(9):669-684. doi: 10.2217/pgs-2019-0015.

Abstract

The ANKS1B gene was a top finding in genome-wide association studies (GWAS) of antipsychotic drug response. Subsequent GWAS findings for ANKS1B include cognitive ability, educational attainment, body mass index, response to corticosteroids and drug dependence. We review current human association evidence for ANKS1B, in addition to functional studies that include two published mouse knockouts. The several GWAS findings in humans indicate that phenotypically relevant variation is segregating at the ANKS1B locus. ANKS1B shows strong plausibility for involvement in CNS drug response because it encodes a postsynaptic effector protein that mediates long-term changes to neuronal biology. Forthcoming data from large biobanks should further delineate the role of ANKS1B in CNS drug response.

Keywords: BMI; NMDA; antipsychotics; cognition; corticosteroids; drugs of abuse; glutamatergic neurotransmission; postsynaptic density; serotonin; synapse to nucleus communication; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Brain / metabolism
  • Central Nervous System Agents / administration & dosage
  • Central Nervous System Agents / pharmacokinetics
  • Central Nervous System Agents / pharmacology*
  • Epigenesis, Genetic
  • Genome-Wide Association Study
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice, Knockout
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism

Substances

  • ANKS1B protein, human
  • Anks1b protein, mouse
  • Central Nervous System Agents
  • Intracellular Signaling Peptides and Proteins