The impact of population admixture on traditional linkage analysis

Jill S. Barnholtz-Sloan, Mariza De Andrade, Ranajit Chakraborty

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Introduction: Families of admixed ancestry are routinely excluded from traditional (Log of the Odds [LOD] score) linkage analysis or are analyzed as being derived from a homogeneous population using the proband's ethnicity. Using traditional linkage analysis with these families can cause complications due to the mixing of different disease rates and allele frequencies that occurs. The presence of admixture violates the key assumptions of Hardy-Weinberg Equilibrium (HWE) and Linkage Equilibrium (LE) invoked in the current methods of linkage analysis. If one or more of these assumptions are violated, incorrect inference for linkage could result. Design and Methods: Through simulation, we investigated the effect of admixture of two populations on the LOD score under various conditions, using prostate cancer as our underlying disease model. Four-generation homogeneous and admixed families were simulated with 27 markers and two linked, bi-allelic disease loci. Two different types of admixture were tested: admixture within a family unit and a mixture of homogeneous families within a data set. All mixing was done at the founder level in three different proportions: 30/70, 50/50 and 70/30. Results and Conclusions: We observed that the LOD scores under both models of admixture were closest to the homogeneous family scores of the population having the highest mixing proportion. Random sampling of families or ascertainment of families with disease affection status did not affect this observation, nor did the mode of inheritance (dominant/recessive) or sample size. Thus, the presence of families of mixed population ancestry impacts linkage analysis in terms of the LOD score and the estimate of the recombination fraction.

Original languageEnglish (US)
Pages (from-to)519-531
Number of pages13
JournalEthnicity and Disease
Volume11
Issue number3
StatePublished - Sep 2001

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Population
Gene Frequency
Sample Size
Genetic Recombination
Prostatic Neoplasms
Datasets

Keywords

  • Hardy-Weinberg Equilibrium
  • Linkage Disequilibrium
  • LOD Score
  • Population Admixture

ASJC Scopus subject areas

  • Medicine(all)
  • Public Health, Environmental and Occupational Health

Cite this

Barnholtz-Sloan, J. S., De Andrade, M., & Chakraborty, R. (2001). The impact of population admixture on traditional linkage analysis. Ethnicity and Disease, 11(3), 519-531.

The impact of population admixture on traditional linkage analysis. / Barnholtz-Sloan, Jill S.; De Andrade, Mariza; Chakraborty, Ranajit.

In: Ethnicity and Disease, Vol. 11, No. 3, 09.2001, p. 519-531.

Research output: Contribution to journalArticle

Barnholtz-Sloan, JS, De Andrade, M & Chakraborty, R 2001, 'The impact of population admixture on traditional linkage analysis', Ethnicity and Disease, vol. 11, no. 3, pp. 519-531.
Barnholtz-Sloan, Jill S. ; De Andrade, Mariza ; Chakraborty, Ranajit. / The impact of population admixture on traditional linkage analysis. In: Ethnicity and Disease. 2001 ; Vol. 11, No. 3. pp. 519-531.
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