Analysis of HLA haplotype distributions in relation to major affective disorder in affected sibling pairs and affected aunt or uncle and niece or nephew pairs confirmed that HLA-region genes do contribute to susceptibility to affective disorder. The data indicated that this effect may be greater in unipolar than in bipolar disorder, and more apparent in families with few affected members than in heavily loaded families. Nonrandom assortment of HLA haplotypes to affected and unaffected offspring in "low load" families occurred principally for the haplotype transmitted from the side of the family without affective disorder. We conclude that HLA-region genes contribute to but are not the only factor in susceptibility to major depression.
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