An extension of the Regression of Offspring on Mid-Parent to test for association and estimate locus-specific heritability: The revised ROMP method

M. H. Roy-Gagnon, R. A. Mathias, M. D. Fallin, S. H. Jee, K. W. Broman, Alexander F. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMPrev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMPrev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest. ROMPrev wasapplied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMPrev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.

Original languageEnglish (US)
Pages (from-to)115-125
Number of pages11
JournalAnnals of Human Genetics
Volume72
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Association tests
  • Candidate gene
  • Cardiovascular disease
  • Parent-offspring trios
  • Quantitative trait

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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