Abstract
Whole-genome association studies are predicted to be especially powerful in isolated populations owing to increased linkage disequilibrium (LD) and decreased allelic diversity, but this possibility has not been empirically tested1,2,3. We compared genome-wide data on 113,240 SNPs typed on 30 trios from the Pacific island of Kosrae to the same markers typed in the 270 samples from the International HapMap Project4,5. The extent of LD is longer and haplotype diversity is lower in Kosrae than in the HapMap populations. More than 98% of Kosraen haplotypes are present in HapMap populations, indicating that HapMap will be useful for genetic studies on Kosrae. The long-range LD around common alleles and limited diversity result in improved efficiency in genetic studies in this population and augments the power to detect association of 'hidden SNPs'.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
de la Chapelle, A. & Wright, F.A. Linkage disequilibrium mapping in isolated populations: the example of Finland revisited. Proc. Natl. Acad. Sci. USA 95, 12416–12423 (1998).
Shifman, S. & Darvasi, A. The value of isolated populations. Nat. Genet. 28, 309–310 (2001).
Wright, A.F., Carothers, A.D. & Pirastu, M. Population choice in mapping genes for complex diseases. Nat. Genet. 23, 397–404 (1999).
the International HapMap Consortium. The International HapMap Project. Nature 426, 789–796 (2003).
The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299–1320 (2005).
Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).
Jorde, L.B. Linkage disequilibrium as a gene-mapping tool. Am. J. Hum. Genet. 56, 11–14 (1995).
Lee, N. et al. A genomewide linkage-disequilibrium scan localizes the Saguenay-Lac-Saint-Jean cytochrome oxidase deficiency to 2p16. Am. J. Hum. Genet. 68, 397–409 (2001).
Eaves, I.A. 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).
Shifman, S., Kuypers, J., Kokoris, M., Yakir, B. & Darvasi, A. Linkage disequilibrium patterns of the human genome across populations. Hum. Mol. Genet. 12, 771–776 (2003).
Kruglyak, L. Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nat. Genet. 22, 139–144 (1999).
Laan, M. & Paabo, S. Demographic history and linkage disequilibrium in human populations. Nat. Genet. 17, 435–438 (1997).
Angius, A. et al. Not all isolates are equal: linkage disequilibrium analysis on Xq13.3 reveals different patterns in Sardinian sub-populations. Hum. Genet. 111, 9–15 (2002).
Shmulewitz, D. et al. Linkage analysis of quantitative traits related to obesity, type II diabetes, hypertentsion and dyslipidemia (metabolic syndrome) on the island of Kosrae, Federated States of Micronesia. Proc. Natl. Acad. Sci. USA (accepted).
Segal, H.G. Kosrae: The Sleeping Lady Awakens (Kosrae State Tourist Division, Department of Conservation and Development, Kosrae State Government, Federated States of Micronesia, 1995).
Reich, D.E. et al. Linkage disequilibrium in the human genome. Nature 411, 199–204 (2001).
Carlson, C.S., Eberle, M.A., Kruglyak, L. & Nickerson, D.A. Mapping complex disease loci in whole-genome association studies. Nature 429, 446–452 (2004).
Lin, S., Chakravarti, A. & Cutler, D.J. Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies. Nat. Genet. 36, 1181–1188 (2004).
Patterson, N. et al. Methods for high-density admixture mapping of disease genes. Am. J. Hum. Genet. 74, 979–1000 (2004).
Spielman, R.S., McGinnis, R.E. & Ewens, W.J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–516 (1993).
Churchill, G.A. & Doerge, R.W. Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971 (1994).
Doerge, R.W. & Churchill, G.A. Permutation tests for multiple loci affecting a quantitative character. Genetics 142, 285–294 (1996).
Van Steen, K. et al. Genomic screening and replication using the same data set in family-based association testing. Nat. Genet. 37, 683–691 (2005).
Wilk, J.B. et al. Family-based association tests for qualitative and quantitative traits using single-nucleotide polymorphism and microsatellite data. Genet. Epidemiol. 21 (Suppl. 1), S364–S369 (2001).
Zhang, J., Schneider, D., Ober, C. & McPeek, M.S. Multilocus linkage disequilibrium mapping by the decay of haplotype sharing with samples of related individuals. Genet. Epidemiol. 29, 128–140 (2005).
Ober, C., Abney, M. & McPeek, M.S. The genetic dissection of complex traits in a founder population. Am. J. Hum. Genet. 69, 1068–1079 (2001).
Barrett, J.C., Fry, B., Maller, J. & Daly, M.J. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265 (2005).
Acknowledgements
We thank M. Sullivan for technical assistance and R. Ferrell for the Beni samples. We thank the Government and Department of Health of Kosrae for their partnership and the people of Kosrae for making this study possible. The authors thank The Starr Foundation for their support.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Bonnen, P., Pe'er, I., Plenge, R. et al. Evaluating potential for whole-genome studies in Kosrae, an isolated population in Micronesia. Nat Genet 38, 214–217 (2006). https://doi.org/10.1038/ng1712
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng1712
This article is cited by
-
The genetic diversity, individual relatedness and possible mating system of an isolated population of the Cyprinid species Megalobrama pellgrini in upper reaches of the Changjiang (Yangtze) River, China
Journal of Oceanology and Limnology (2019)
-
Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population
Scientific Reports (2015)
-
Implications for health and disease in the genetic signature of the Ashkenazi Jewish population
Genome Biology (2012)
-
European admixture on the Micronesian island of Kosrae: lessons from complete genetic information
European Journal of Human Genetics (2010)
-
Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami
European Journal of Human Genetics (2010)