A permutation test for the robust sib-pair linkage method.
The robust sib-pair method introduced by Haseman & 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.
Wan
Y
Y
Department of Statistical Science, Southern Methodist University, Dallas, Texas 75275, USA.
Cohen
J
J
Guerra
R
R
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics; D008078:Cholesterol, LDL / Q000235:genetics; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008957:Models, Genetic; D013223:Statistics as Topic
D001053:Apolipoproteins; D008078:Cholesterol, LDL