Immunogenetics

, Volume 64, Issue 2, pp 97–109

KIR genotypic diversity can track ancestries in heterogeneous populations: a potential confounder for disease association studies

  • Komal Manpreet Singh
  • Yume T. Phung
  • Mohamed S. Kohla
  • Billy Y-A Lan
  • Sharon Chan
  • Diana L. Suen
  • Sahar Murad
  • Shana Rheault
  • Peter Davidson
  • Jennifer Evans
  • Manpreet Singh
  • Sofie Dohil
  • Robert W. Osorio
  • Adil E. Wakil
  • Kimberly Page
  • Sandy Feng
  • Stewart L. Cooper
Original Paper

DOI: 10.1007/s00251-011-0569-x

Cite this article as:
Singh, K.M., Phung, Y.T., Kohla, M.S. et al. Immunogenetics (2012) 64: 97. doi:10.1007/s00251-011-0569-x

Abstract

Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic genes that regulate the activation of natural killer (NK) cells and other lymphocyte subsets and likely play key roles in innate and adaptive immunity. Association studies increasingly implicate KIR in disease predisposition and outcome but could be confounded by unknown KIR genetic structure in heterogeneous populations. To examine this, we characterized the diversity of 16 KIR genes in 712 Northern Californians (NC) stratified by self-assigned ethnicities and compared the profiles of KIR polymorphism with other US and global populations using a reference database. Sixty-eight distinct KIR genotypes were characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21 in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 “other” ethnicities (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were compared with each other and with 34 global populations by phylogenetic analysis. Although there were no population-specific genotypes, the KIR genotype frequency patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH whose ancestries are known to be more heterogeneous. KIR genotype frequencies can therefore track ethnic ancestries in modern urban populations. Our data emphasize the importance of selecting ethnically matched controls in KIR-based studies to avert spurious associations.

Keywords

KIR genotype frequencyPolymorphismNorthern California populationEthnicity

Supplementary material

251_2011_569_MOESM1_ESM.pdf (95 kb)
Supplementary Figure 1Phylogenetic tree constructed using KIR genotype frequencies of major ethnicities sampled in Northern California (PDF 95.3 kb)
251_2011_569_MOESM2_ESM.pdf (116 kb)
Supplementary Figure 2Individual KIR Gene Frequencies in California (PDF 116 kb)
251_2011_569_MOESM3_ESM.pdf (123 kb)
Supplementary Table 1KIR genotype analysis within California (PDF 122 kb)
251_2011_569_MOESM4_ESM.pdf (132 kb)
Supplementary Table 2KIR alleles potentially undetected by the typing system (PDF 131 kb)

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Komal Manpreet Singh
    • 1
  • Yume T. Phung
    • 1
  • Mohamed S. Kohla
    • 1
    • 7
  • Billy Y-A Lan
    • 5
  • Sharon Chan
    • 5
  • Diana L. Suen
    • 1
  • Sahar Murad
    • 1
    • 3
  • Shana Rheault
    • 1
  • Peter Davidson
    • 6
  • Jennifer Evans
    • 6
  • Manpreet Singh
    • 8
  • Sofie Dohil
    • 1
  • Robert W. Osorio
    • 3
  • Adil E. Wakil
    • 1
    • 2
    • 3
  • Kimberly Page
    • 6
  • Sandy Feng
    • 4
    • 5
  • Stewart L. Cooper
    • 1
    • 2
    • 3
    • 4
  1. 1.Kalmanovitz Liver Immunology LaboratoryCalifornia Pacific Medical Center & Research InstituteSan FranciscoUSA
  2. 2.Division of HepatologyCalifornia Pacific Medical Center & Sutter Pacific Medical FoundationSan FranciscoUSA
  3. 3.Department of TransplantationCalifornia Pacific Medical CenterSan FranciscoUSA
  4. 4.UCSF Liver CenterSan FranciscoUSA
  5. 5.Department of TransplantationUniversity of California, San FranciscoSan FranciscoUSA
  6. 6.Department of EpidemiologyUniversity of California, San FranciscoSan FranciscoUSA
  7. 7.The National Liver InstituteMenoufiyaEgypt
  8. 8.