Polygenic heritability estimates in pharmacogenetics: Focus on asthma and related phenotypes

Michael J. Mcgeachie, Eli A. Stahl, Blanca E. Himes, Sarah A. Pendergrass, John J. Lima, Charles G. Irvin, Stephen P. Peters, Marylyn D. Ritchie, Robert M. Plenge, Kelan G. Tantisira

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Although accurate measures of heritability are required to understand the pharmacogenetic basis of drug treatment response, these are generally not available, as it is unfeasible to give medications to individuals for which treatment is not indicated. Using a polygenic linear mixed modeling approach, we estimated lower bounds on the heritability of asthma and the heritability of two related drug-response phenotypes, bronchodilator response and airway hyperreactivity, using genome-wide single nucleotide polymorphism (SNP) data from existing asthma cohorts. Our estimate of the heritability for bronchodilator response is 28.5% (SE 16%, P= 0.043) and airway hyperresponsiveness is 51.1% (SE 34%, P = 0.064), whereas we estimate asthma genetic liability at 61.5% (SE 16%, P > 0.001). Our results agree with the previously published estimates of the heritability of these traits, suggesting that the linear mixed modeling method is useful for computing the heritability of other pharmacogenetic traits. Furthermore, our results indicate that multiple SNP main effects, including SNPs as yet unidentified by genome-wide association study methods, together explain a sizable portion of the heritability of these traits.

Original languageEnglish (US)
Pages (from-to)324-328
Number of pages5
JournalPharmacogenetics and Genomics
Volume23
Issue number6
DOIs
StatePublished - Jun 1 2013

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Mcgeachie, M. J., Stahl, E. A., Himes, B. E., Pendergrass, S. A., Lima, J. J., Irvin, C. G., Peters, S. P., Ritchie, M. D., Plenge, R. M., & Tantisira, K. G. (2013). Polygenic heritability estimates in pharmacogenetics: Focus on asthma and related phenotypes. Pharmacogenetics and Genomics, 23(6), 324-328. https://doi.org/10.1097/FPC.0b013e3283607acf