A genome-wide scan for type 1 diabetes susceptibility genes in nuclear families with multiple affected siblings in Finland

BACKGROUND: A genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk HLA haplotypes that include DR3 or DR4 alleles. RESULTS: In addition to the evidence of linkage to the HLA region on 6p21 (nominal p = 4.0 × 10(-6)), significant evidence of linkage in other chromosome regions was not detected with a single-locus analysis. The two-locus analysis conditional on the HLA gave a maximum lod score (MLS) of 3.1 (nominal p = 2 × 10(-4)) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p = 6.1 × 10(-3)) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 × 10(-3)) on chromosome 18p11 under a general model. CONCLUSION: Our genome scan data confirmed the primary contribution of the HLA genes also in the high-risk Finnish population, and suggest that non-HLA genes also contribute to the familial clustering of type 1 diabetes in Finland.