Confirmation of the relationship of HLA (chromosome 6) genes to depression and manic depression. II. The Ontario follow-up and analysis of 117 kindreds.
HLA typing was conducted on 577 family members of 86 families having at least two first-degree family members with a lifetime history of major depression or bipolar disorder. The results were combined with a follow-up study of 10 Newfoundland kindreds and with the data obtained from our previous studies, giving a total cohort of 117 families of diverse ethnic and geographic origin. There was increased sharing of HLA haplotypes, as compared with random expectation, over all possible pairwise comparisons both in the follow-up studies (P less than 0.025) and in the total data (P less than 0.01). The increase in HLA haplotype sharing over random expectation was greater if comparisons within heavily loaded sibships (by prior convention, sibships with three or more affected siblings) were omitted from the analysis (P less than 0.002). There was also non-random transmission of HLA haplotypes in 50 families selected for a low-load, unaffected parent (P less than 0.005). Thus, we conclude that genes in the HLA region of chromosome 6 constitute one of the elements in the multifactorial etiology of affective disorder. This conclusion does not depend on any assumption concerning genetic heterogeneity or epistasis or on specific modes of transmission, penetrance values or linkage distances. In addition, the data suggest that chromosome 6 region genes may have a different effect in unipolar and bipolar illness.
Stancer
H C
HC
Clarke Institute of Psychiatry, Department of Psychiatry, University of Toronto, Canada.
Weitkamp
L R
LR
Persad
E
E
Flood
C
C
Jorna
T
T
Guttormsen
S A
SA
Yagnow
R L
RL
D001714:Bipolar Disorder / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D003866:Depressive Disorder / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005805:Genes, MHC Class I; D015235:HLA-B Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D010375:Pedigree
D015235:HLA-B Antigens