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Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.

Publication ,  Journal Article
Abo, R; Hebbring, S; Ji, Y; Zhu, H; Zeng, Z-B; Batzler, A; Jenkins, GD; Biernacka, J; Snyder, K; Drews, M; Fiehn, O; Fridley, B; Schaid, D ...
Published in: Pharmacogenet Genomics
April 2012

OBJECTIVE: We set out to test the hypothesis that pharmacometabolomic data could be efficiently merged with pharmacogenomic data by single-nucleotide polymorphism (SNP) imputation of metabolomic-derived pathway data on a 'scaffolding' of genome-wide association (GWAS) SNP data to broaden and accelerate 'pharmacometabolomics-informed pharmacogenomic' studies by eliminating the need for initial genotyping and by making broader SNP association testing possible. METHODS: We previously genotyped 131 tag SNPs for six genes encoding enzymes in the glycine synthesis and degradation pathway using DNA from 529 depressed patients treated with citalopram/escitalopram to pursue a glycine metabolomics 'signal' associated with selective serotonine reuptake inhibitor response. We identified a significant SNP in the glycine dehydrogenase gene. Subsequently, GWAS SNP data were generated for the same patients. In this study, we compared SNP imputation within 200 kb of these same six genes with the results of the previous tag SNP strategy as a rapid strategy for merging pharmacometabolomic and pharmacogenomic data. RESULTS: Imputed genotype data provided greater coverage and higher resolution than did tag SNP genotyping, with a higher average genotype concordance between genotyped and imputed SNP data for '1000 Genomes' (96.4%) than HapMap 2 (93.2%) imputation. Many low P-value SNPs with novel locations within genes were observed for imputed compared with tag SNPs, thus altering the focus for subsequent functional genomic studies. CONCLUSION: These results indicate that the use of GWAS data to impute SNPs for genes in pathways identified by other 'omics' approaches makes it possible to rapidly and cost efficiently identify SNP markers to 'broaden' and accelerate pharmacogenomic studies.

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Published In

Pharmacogenet Genomics

DOI

EISSN

1744-6880

Publication Date

April 2012

Volume

22

Issue

4

Start / End Page

247 / 253

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Metabolomics
  • Metabolic Networks and Pathways
  • Humans
  • Haplotypes
  • HapMap Project
  • Glycine Dehydrogenase
 

Citation

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Abo, R., Hebbring, S., Ji, Y., Zhu, H., Zeng, Z.-B., Batzler, A., … Weinshilboum, R. M. (2012). Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics. Pharmacogenet Genomics, 22(4), 247–253. https://doi.org/10.1097/FPC.0b013e32835001c9
Abo, Ryan, Scott Hebbring, Yuan Ji, Hongjie Zhu, Zhao-Bang Zeng, Anthony Batzler, Gregory D. Jenkins, et al. “Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.Pharmacogenet Genomics 22, no. 4 (April 2012): 247–53. https://doi.org/10.1097/FPC.0b013e32835001c9.
Abo, Ryan, et al. “Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics.Pharmacogenet Genomics, vol. 22, no. 4, Apr. 2012, pp. 247–53. Pubmed, doi:10.1097/FPC.0b013e32835001c9.
Abo R, Hebbring S, Ji Y, Zhu H, Zeng Z-B, Batzler A, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Fridley B, Schaid D, Kamatani N, Nakamura Y, Kubo M, Mushiroda T, Kaddurah-Daouk R, Mrazek DA, Weinshilboum RM. Merging pharmacometabolomics with pharmacogenomics using '1000 Genomes' single-nucleotide polymorphism imputation: selective serotonin reuptake inhibitor response pharmacogenomics. Pharmacogenet Genomics. 2012 Apr;22(4):247–253.

Published In

Pharmacogenet Genomics

DOI

EISSN

1744-6880

Publication Date

April 2012

Volume

22

Issue

4

Start / End Page

247 / 253

Location

United States

Related Subject Headings

  • Selective Serotonin Reuptake Inhibitors
  • Polymorphism, Single Nucleotide
  • Pharmacology & Pharmacy
  • Pharmacogenetics
  • Metabolomics
  • Metabolic Networks and Pathways
  • Humans
  • Haplotypes
  • HapMap Project
  • Glycine Dehydrogenase