Human leukocyte antigen system not closely linked to or associated with bipolar manic-depressive illness

An association and linkage study of the HLA system and bipolar affective illness is reported. HLA B-14 showed an increased frequency and HLA-Bw27 a decreased frequency in 92 bipolar patients compared to 210 controls, but significance is not reached when appropriate statistical corrections are made. It is shown that ethnological differences can lead to sampling biases; a purported increased frequency of HLA-Bw 16 in Ashkenazi Jewish bipolar patients is negated when ethnologically similar controls are used. The transmission of HLA alleles in nine families with at least two generations of affective illness revealed independent assortment, and nonlinkage to either locus A or B was demonstrated using a multigenerational method of linkage analysis. The nonreplicability of the HLA association studies, and the failure to demonstrate linkage of the HLA loci with afe development of affective illness, although further analyses are necessary.