LINKAGE OF TYPE-I DIABETES TO 15Q26 (IDDM3) IN THE DANISH POPULATION

Affected sib pair and linkage disequilibrium analysis, intrafamilial a nd case-control association studies were performed on 81 Danish multip lex insulin-dependent diabetes mellitus (IDDM) families (382 individua ls) and 82 healthy Danish controls. The results confirm the linkage of D15S107 to IDDM in these Danish IDDM families (P = 0.010). When these data are combined with those of previous studies, an even stronger ca se for linkage can be made (P = 0.0005). Our analyses show that the D1 5S107130 allele provides increased susceptibility (P = 0.02, relative risk = 3.55) and that the D15S107 locus contributes up to 16% of the familial clustering of IDDM. The analysis of affected sib pairs sugges ts that HLA and D15S107 may possibly act independently of each other. Taken together with our previous findings, our results suggest that th ree causes of susceptibilities can be discerned in the IDDM patient po pulation: (1) a major susceptibility caused by the HLA-DRB1 alleles; ( 2) a minor susceptibility caused by the joint action of HLA and other non-HLA gene(s); and (3) a minor susceptibility caused by non-HLA gene (s).