Research article

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

Qing Qiao^{* 1,2} , Anne-May Österholm^{* 3} , Bing He^{* 3} , Janne Pitkäniemi^1,2 , Heather J Cordell⁴ , Cinzia Sarti¹ , Leena Kinnunen^1,2 , Eva Tuomilehto-Wolf¹ , Karl Tryggvason³ and Jaakko Tuomilehto^1,2,5

¹Department of Public Health, University of Helsinki, Finland

²Diabetes Unit, Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland

³Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden

⁴Institute of Human Genetics, Newcastle University, UK

⁵South Ostrobothnia Central Hospital, Seinäjoki, Finland

author email corresponding author email* Contributed equally

BMC Genetics 2007, 8:84doi:10.1186/1471-2156-8-84

Published:	19 December 2007

Abstract

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.