Extent and distribution of linkage disequilibrium in the old order amish

Cristopher V. Van Hout, Albert M. Levin, Evadnie Rampersaud, Haiqing Shen, Jeffrey R. O'Connell, Braxton D. Mitchell, Alan R. Shuldiner, Julie A. Douglas

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)146-150
Number of pages5
JournalGenetic Epidemiology
Volume34
Issue number2
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • Founder population
  • Haplotypes
  • Human genetics
  • Linkage disequilibrium
  • Population genetics
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

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