The ANKS1B Gene and its Associated Phenotypes: Focus on CNS Drug Response

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::

• antipsychotics
• BMI
• cognition
• corticosteroids
• drugs of abuse
• glutamatergic neurotransmission
• NMDA
• postsynaptic density
• serotonin
• synapse to nucleus communication
• synaptic plasticity

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Material has been reviewed by the Walter Reed Army Institute of Research. There is no objectionto its presentation and/or publication. The opinions or assertions contained herein are the private views of theauthor, and are not to be construed as official, or as reflecting true views of the Department of the Army or theDepartment of Defense.

Financial & competing interests disclosure

RM Younis was funded through a graduate studentship from Virginia Commonwealth University (VCU) School of Pharmacy and this review was completed in partial fulfillment of the doctoral requirements in Pharmaceutical Sciences at VCU. This work was funded through a pilot award from the Endowment Fund of the Wright Center for Clinical and Translational Research at VCU and UL1TR000058 from the National Center for Advancing Translational Sciences. JL McClay was partially supported by National Institute of Mental Health grant R56MH107879. PM Beardsley was supported by NIDA N01DA-14-8917, NIDA N01DA-17-8932 and DOJ D-17-OD-0092. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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Funding

Financial & competing interests disclosure RM Younis was funded through a graduate studentship from Virginia Commonwealth University (VCU) School of Pharmacy and this review was completed in partial fulfillment of the doctoral requirements in Pharmaceutical Sciences at VCU. This work was funded through a pilot award from the Endowment Fund of the Wright Center for Clinical and Translational Research at VCU and UL1TR000058 from the National Center for Advancing Translational Sciences. JL McClay was partially supported by National Institute of Mental Health grant R56MH107879. PM Beardsley was supported by NIDA N01DA-14-8917, NIDA N01DA-17-8932 and DOJ D-17-OD-0092. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.