A permutation test for the robust sib-pair linkage method

Y. Wan, J. Cohen, R. Guerra

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The robust sib-pair method introduced by Haseman and Elston (1972) is one of the most widely circulated allele-sharing methods for linkage analysis. The procedure evaluates linkage by significance testing of a regression coefficient and, hence, a standard t-test has traditionally been applied despite known violations of the statistical assumptions underlying the test. We present a permutation based reference distribution for the estimate of the regression coefficient that is motivated by genetic principles rather than by standard regression testing procedures. The permutation test approximates Mendelian co-segregation under the null hypothesis of no linkage, making it a very natural approach. Theory and simulations show that the conventional t-test approximates the permutation test quite well, even when dependent sib pairs are used for analysis. These results thus indirectly address concerns over the t-test. To illustrate the permutation test using real data we applied the procedure to two lipoprotein systems that have been well characterized.

Original languageEnglish (US)
Pages (from-to)77-85
Number of pages9
JournalAnnals of Human Genetics
Volume61
Issue number1
DOIs
StatePublished - Jan 1997

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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