Open Access Research article

Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

Elena Bosch12*, Hafid Laayouni12, Carlos Morcillo-Suarez13, Ferran Casals14, Andrés Moreno-Estrada1, Anna Ferrer-Admetlla1, Michelle Gardner12, Araceli Rosa1, Arcadi Navarro135, David Comas12, Jan Graffelman6, Francesc Calafell12 and Jaume Bertranpetit12

Author Affiliations

1 Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain

2 CIBER de Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

3 National Institute for Bioinformatics (INB), Population Genomics Node, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain

4 Department of Pediatric, Ste Justine Hospital Research Centre, Faculty of Medicine, University of Montreal, Montreal, Quebec H3T 1C5, Canada

5 Institució Catalana de Recerca i Estudis Avançats (ICREA), Universitat Pompeu Fabra, Barcelona, Spain

6 Department of Statistics and Operations Research, Universitat Politècnica de Catalunya, Barcelona, Spain

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BMC Genomics 2009, 10:338  doi:10.1186/1471-2164-10-338

Published: 28 July 2009



It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8.


Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates.


The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.