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Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.

Publication ,  Journal Article
Adkins, DE; Aberg, K; McClay, JL; Bukszár, J; Zhao, Z; Jia, P; Stroup, TS; Perkins, D; McEvoy, JP; Lieberman, JA; Sullivan, PF; van den Oord, EJCG
Published in: Mol Psychiatry
March 2011

Understanding individual differences in the susceptibility to metabolic side effects as a response to antipsychotic therapy is essential to optimize the treatment of schizophrenia. Here, we perform genomewide association studies (GWAS) to search for genetic variation affecting the susceptibility to metabolic side effects. The analysis sample consisted of 738 schizophrenia patients, successfully genotyped for 492K single nucleotide polymorphisms (SNPs), from the genomic subsample of the Clinical Antipsychotic Trial of Intervention Effectiveness study. Outcomes included 12 indicators of metabolic side effects, quantifying antipsychotic-induced change in weight, blood lipids, glucose and hemoglobin A1c, blood pressure and heart rate. Our criterion for genomewide significance was a pre-specified threshold that ensures, on average, only 10% of the significant findings are false discoveries. A total of 21 SNPs satisfied this criterion. The top finding indicated that a SNP in Meis homeobox 2 (MEIS2) mediated the effects of risperidone on hip circumference (q=0.004). The same SNP was also found to mediate risperidone's effect on waist circumference (q=0.055). Genomewide significant finding were also found for SNPs in PRKAR2B, GPR98, FHOD3, RNF144A, ASTN2, SOX5 and ATF7IP2, as well as in several intergenic markers. PRKAR2B and MEIS2 both have previous research indicating metabolic involvement, and PRKAR2B has previously been shown to mediate antipsychotic response. Although our findings require replication and functional validation, this study shows the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antipsychotic medication.

Duke Scholars

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Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

March 2011

Volume

16

Issue

3

Start / End Page

321 / 332

Location

England

Related Subject Headings

  • Waist Circumference
  • Treatment Outcome
  • Transcription Factors
  • Schizophrenia
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Metabolic Diseases
  • Male
 

Citation

APA
Chicago
ICMJE
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Adkins, D. E., Aberg, K., McClay, J. L., Bukszár, J., Zhao, Z., Jia, P., … van den Oord, E. J. C. G. (2011). Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol Psychiatry, 16(3), 321–332. https://doi.org/10.1038/mp.2010.14
Adkins, D. E., K. Aberg, J. L. McClay, J. Bukszár, Z. Zhao, P. Jia, T. S. Stroup, et al. “Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.Mol Psychiatry 16, no. 3 (March 2011): 321–32. https://doi.org/10.1038/mp.2010.14.
Adkins DE, Aberg K, McClay JL, Bukszár J, Zhao Z, Jia P, et al. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol Psychiatry. 2011 Mar;16(3):321–32.
Adkins, D. E., et al. “Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs.Mol Psychiatry, vol. 16, no. 3, Mar. 2011, pp. 321–32. Pubmed, doi:10.1038/mp.2010.14.
Adkins DE, Aberg K, McClay JL, Bukszár J, Zhao Z, Jia P, Stroup TS, Perkins D, McEvoy JP, Lieberman JA, Sullivan PF, van den Oord EJCG. Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs. Mol Psychiatry. 2011 Mar;16(3):321–332.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

March 2011

Volume

16

Issue

3

Start / End Page

321 / 332

Location

England

Related Subject Headings

  • Waist Circumference
  • Treatment Outcome
  • Transcription Factors
  • Schizophrenia
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Pharmacogenetics
  • Middle Aged
  • Metabolic Diseases
  • Male