title: Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut de Biologia Evolutiva (UPF-CSIC), Departament de Ciències Experimentals i de Salut, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain. elena.bosch@upf.edu
authors.forename: Elena
authors.initials: E
authors.lastname: Bosch
authors.forename: Hafid
authors.initials: H
authors.lastname: Laayouni
authors.forename: Carlos
authors.initials: C
authors.lastname: Morcillo-Suarez
authors.forename: Ferran
authors.initials: F
authors.lastname: Casals
authors.forename: Andrés
authors.initials: A
authors.lastname: Moreno-Estrada
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrer-Admetlla
authors.forename: Michelle
authors.initials: M
authors.lastname: Gardner
authors.forename: Araceli
authors.initials: A
authors.lastname: Rosa
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.forename: David
authors.initials: D
authors.lastname: Comas
authors.forename: Jan
authors.initials: J
authors.lastname: Graffelman
authors.forename: Francesc
authors.initials: F
authors.lastname: Calafell
authors.forename: Jaume
authors.initials: J
authors.lastname: Bertranpetit
mesh_terms: D002460:Cell Line; D005828:Genetics, Population; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D017422:Sequence Analysis, DNA