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 x 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 x 10-4) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p = 6.1 x 10-3) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 x 10-3) on chromosome 18p11 under a general model.


CONCLUSIONS
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.
Qiao
Qing
Q
Department of Public Health, University of Helsinki, Finland. qing.qiao@ktl.fi
Osterholm
Anne-May
AM
He
Bing
B
Pitkäniemi
Janne
J
Cordell
Heather J
HJ
Sarti
Cinzia
C
Kinnunen
Leena
L
Tuomilehto-Wolf
Eva
E
Tryggvason
Karl
K
Tuomilehto
Jaakko
J
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005387:Finland; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D008875:Middle Aged; D009679:Nuclear Family; D035781:Siblings