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The genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes

Nature Genetics volume 25, pages 320–323 (2000)Cite this article

Abstract

The choice of which population to study in the mapping of common disease genes may be critical1,2. Isolated founder populations, such as that found in Finland, have already proved extremely useful for mapping the genes for specific rare monogenic disorders3,4 and are being used in attempts to map the genes underlying common, complex diseases5,6,7,8. But simulation results suggest that, under the common disease-common variant hypothesis9,10,11,12,13, most isolated populations will prove no more useful for linkage disequilibrium (LD) mapping of common disease genes than large outbred populations12. There is very little empirical data to either support or refute this conclusion at present14,15,16. Therefore, we evaluated LD between 21 common microsatellite polymorphisms on chromosome 18q21 in 2 genetic isolates (Finland and Sardinia) and compared the results with those observed in two mixed populations (United Kingdom and United States of America). Mean levels of LD were similar across all four populations. Our results provide empirical support for the expectation that genetic isolates like Finland and Sardinia will not prove significantly more valuable than general populations for LD mapping of common variants underlying complex disease.

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Figure 1: Relationship between mean level of LD and marker separation for the four populations studied.
Figure 2: Relationship between mean level of LD and marker separation after classifying alleles into two groups.
Figure 3: Distribution of d2 values for marker separations of ≤1 cM.

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Acknowledgements

This work was funded by the Wellcome Trust, British Diabetic Association (BDA), UK Medical Research Council and the Juvenile Diabetes Foundation International. We are grateful for the assistance of the ‘Childhood Diabetes in Finland (DiMe) Study Group’ in the collection of the Finnish family material. The Finnish family collaboration was partially funded by grants from NIH (DK 73957) and the Novo Nordisk Foundation. The BDA and the Human Biological Data Interchange are thanked for the collection of families. F.C. was supported in part by a grant from Assessorato Igiene e Sanità, Regione Sardegna.

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Authors and Affiliations

  1. Department of Medical Genetics, Wellcome Trust Centre for Molecular Mechanisms in Disease, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Cambridge, UK

    Iain A. Eaves, Sarah Nutland & John A. Todd

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK

    Tony R. Merriman & Rachael A. Barber

  3. Diabetes and Genetic Epidemiology Unit, National Public Health Institute, Helsinki, Finland

    Eva Tuomilehto-Wolf & Jaakko Tuomilehto

  4. Instituto di Clinica e Biologia dell'Eta' Evolutiva, University of Cagliari, Italy

    Francesco Cucca

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  1. Iain A. Eaves
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Correspondence to John A. Todd.

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Eaves, I., Merriman, T., Barber, R. et al. The genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Nat Genet 25, 320–323 (2000). https://doi.org/10.1038/77091

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