Power of association test for detecting minor histocompatibility gene causing graft-versus-host disease following bone barrow transplantation

Incompatibility of minor histocompatibility antigen (mHa) is a major cause of acute graft-versus-host disease (GVHD) following bone marrow transplantation in human leukocyte antigen (HLA)-matched donor-recipient pairs. To avoid acute GVHD, as many mHa genes as possible need to be identified. In this study, we introduce a comparison of two proportions as an association test for detecting mHa genes in HLA-matched pairs with and without GVHD. Assuming multiple mHa loci, each with two alleles, we evaluated the effects of (1). minor allele frequency of the mHa locus of interest (denoted by p), and (2). probability of GVHD developing in a donor-recipient pair being incompatible at an mHa locus (denoted by r) on the powers of association tests for unrelated pairs and for sib pairs. Our results showed that based on a candidate gene approach, an mHa gene with high p and r values can be detected by the association test with a small sample size. Application of the present method to the Japanese population revealed that the association test for unrelated pairs is more suitable for detecting an mHa gene with a high r value than that for sib pairs. The present method will be helpful to researchers who evaluate the power of association study in advance.