The Extent of Linkage Disequilibrium in Four Populations with Distinct Demographic Histories

• Published in: American journal of human genetics 2000-12, Vol.67 (6), p.1544-1554
• Main Authors: Dunning, Alison M., Durocher, Francine, Healey, Catherine S., Teare, M. Dawn, McBride, Simon E., Carlomagno, Francesca, Xu, Chun-Fang, Dawson, Elisabeth, Rhodes, Susan, Ueda, Saeko, Lai, Eric, Luben, Robert N., Van Rensburg, Elizabeth J., Mannermaa, Arto, Kataja, Vesa, Rennart, Gadi, Dunham, Ian, Purvis, Ian, Easton, Douglas, Ponder, Bruce A.J.
• Format: Article
• Language: English
• Subjects: Africa - ethnology; Alleles; Biological and medical sciences; Chromosome Mapping - methods; Chromosomes, Human, Pair 13 - genetics; Chromosomes, Human, Pair 19 - genetics; Chromosomes, Human, Pair 22 - genetics; Demography; Finland - ethnology; Gene Frequency - genetics; General aspects. Genetic counseling; Genetic Markers - genetics; Genetic Predisposition to Disease - genetics; Genotype; Humans; Jews - genetics; Linkage Disequilibrium - genetics; Medical genetics; Medical sciences; Phylogeny; Polymorphism, Genetic - genetics; United Kingdom - ethnology
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/316906

The design and feasibility of whole-genome–association studies are critically dependent on the extent of linkage disequilibrium (LD) between markers. Although there has been extensive theoretical discussion of this, few empirical data exist. The authors have determined the extent of LD among 38 biallelic markers with minor allele frequencies >.1, since these are most comparable to the common disease-susceptibility polymorphisms that association studies aim to detect. The markers come from three chromosomal regions—1,335 kb on chromosome 13q12-13, 380 kb on chromosome 19q13.2, and 120 kb on chromosome 22q13.3—which have been extensively mapped. These markers were examined in ∼1,600 individuals from four populations, all of European origin but with different demographic histories; Afrikaners, Ashkenazim, Finns, and East Anglian British. There are few differences, either in allele frequencies or in LD, among the populations studied. A similar inverse relationship was found between LD and distance in each genomic region and in each population. Mean D′ is .68 for marker pairs 500 kb. However, only 50% of marker pairs at distances .3) to be useful in association studies. Results of the present study, if representative of the whole genome, suggest that a whole-genome scan searching for common disease-susceptibility alleles would require markers spaced ≤5 kb apart.