Allele sharing and allelic association I: sib pair tests with increased power

Affected sib pair data contain information about allele sharing and allelic association. Either of these features can point to the presence of a risk-related gene. This study introduces the elliptical sib pair test, a generalization of traditional sib pair tests. The proposed test can be implemented using any of three strategies, the choice of which depends on the anticipated combination of sharing and association. The elliptical sib pair test can achieve substantial gains in power relative to traditional tests for likely alternative hypotheses at little or no cost for other alternatives. The proposed test is valid under most models of genetic risk, disease etiology, and genotype-haplotype distributions. This study also provides new insight into the trade-off between tests of allelic association and tests of allele sharing.