### Sham PC, Curtis D. Monte Carlo tests for associations between
disease and alleles at highly polymorphic loci. Ann Hum Genet
1995 59: 97-105.

In an association analysis comparing cases and controls with
respect to allele frequencies at a highly polymorphic locus, a
potential problem is that the conventional chi-squared test may
not be valid for a large, sparse contingency table. However,
reliance on statistics with known asymptotic distribution is now
unnecessary, as Monte Carlo simulations can be performed to
estimate the significance level of any test statistic. We have
implemented a Monte Carlo method for four "chi-squared" test
statistics, three of which involving combination of alleles, and
evaluated their performance on a real data set. Combining rare
alleles to avoid small expected cell counts, and considering each
allele in turn against the rest, reduced the power to detect a
genuine association when the number of alleles was very large.
We should either not combine alleles at all, or combine them in
a such way that preserves the evidence for an association.

Dave Curtis publications