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Comparing HLA antigen frequencies between two groups of patients
Author(s) -
Follmann Dean A.
Publication year - 2003
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.1426
Subject(s) - human leukocyte antigen , allele , bonferroni correction , immunology , stage (stratigraphy) , population , cohort , antigen , allele frequency , immune system , medicine , biology , genetics , statistics , mathematics , gene , paleontology , environmental health
For diseases that involve the immune system, the alleles of the human leukocyte antigen (HLA) complex can play a major role. For example, if responsiveness to therapy is immunologically mediated, one would think that responders and non‐responders might tend to have different HLA alleles. However, comparing the frequencies between the two groups of patients at each allele can introduce a substantial multiple comparisons problem as the number of alleles is large. This paper proposes an efficient two‐stage procedure for identifying alleles that may mediate response. In the first‐stage, the distribution of all alleles for the patients are compared to a reference population and a few alleles are selected. These candidate alleles are then compared between the two groups of patients using a modest Bonferroni correction. The two‐stage procedure strongly controls the type I error rate as the first‐stage selection is statistically independent of the second‐stage tests. We analyse a cohort of patients with bone marrow failure who are classified as responders or non‐responders to immunosuppressive therapy. Published in 2003 by John Wiley & Sons, Ltd.