The first two authors contributed equally to this work.
Extent and distribution of linkage disequilibrium in the Old Order Amish
Version of Record online: 20 AUG 2009
© 2009 Wiley-Liss, Inc.
Volume 34, Issue 2, pages 146–150, February 2010
How to Cite
Van Hout, C. V., Levin, A. M., Rampersaud, E., Shen, H., O'Connell, J. R., Mitchell, B. D., Shuldiner, A. R. and Douglas, J. A. (2010), Extent and distribution of linkage disequilibrium in the Old Order Amish. Genet. Epidemiol., 34: 146–150. doi: 10.1002/gepi.20444
- Issue online: 19 JAN 2010
- Version of Record online: 20 AUG 2009
- Manuscript Accepted: 10 JUN 2009
- Manuscript Revised: 14 APR 2009
- Manuscript Received: 27 JAN 2009
- NIH. Grant Numbers: U01 HL72515, R01 CA122844
- single nucleotide polymorphism;
- population genetics;
- human genetics;
- founder population;
- linkage disequilibrium;
Knowledge of the extent and distribution of linkage disequilibrium (LD) is critical to the design and interpretation of gene mapping studies. Because the demographic history of each population varies and is often not accurately known, it is necessary to empirically evaluate LD on a population-specific basis. Here we present the first genome-wide survey of LD in the Old Order Amish (OOA) of Lancaster County Pennsylvania, a closed population derived from a modest number of founders. Specifically, we present a comparison of LD between OOA individuals and US Utah participants in the International HapMap project (abbreviated CEU) using a high-density single nucleotide polymorphism (SNP) map. Overall, the allele (and haplotype) frequency distributions and LD profiles were remarkably similar between these two populations. For example, the median absolute allele frequency difference for autosomal SNPs was 0.05, with an inter-quartile range of 0.02–0.09, and for autosomal SNPs 10–20 kb apart with common alleles (minor allele frequency≥0.05), the LD measure r2 was at least 0.8 for 15 and 14% of SNP pairs in the OOA and CEU, respectively. Moreover, tag SNPs selected from the HapMap CEU sample captured a substantial portion of the common variation in the OOA (∼88%) at r2≥0.8. These results suggest that the OOA and CEU may share similar LD profiles for other common but untyped SNPs. Thus, in the context of the common variant-common disease hypothesis, genetic variants discovered in gene mapping studies in the OOA may generalize to other populations. Genet. Epidemiol. 34: 146–150, 2010. © 2009 Wiley-Liss, Inc.