Human Genetics

, Volume 120, Issue 5, pp 623–631

Localization and replication of the systemic lupus erythematosus linkage signal at 4p16: interaction with 2p11, 12q24 and 19q13 in European Americans

  • Chao Xing
  • Andrea L. Sestak
  • Jennifer A. Kelly
  • Kim L. Nguyen
  • Gail R. Bruner
  • John B. Harley
  • Courtney Gray-McGuire
Original Investigation

DOI: 10.1007/s00439-006-0248-4

Cite this article as:
Xing, C., Sestak, A.L., Kelly, J.A. et al. Hum Genet (2007) 120: 623. doi:10.1007/s00439-006-0248-4

Abstract

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by both population and phenotypic heterogeneity. Our group previously identified linkage to SLE at 4p16 in European Americans (EA). In the present study we replicate this linkage effect in a new cohort of 76 EA families multiplex for SLE by model-free linkage analysis. Using densely spaced microsatellite markers in the linkage region, we have localized the potential SLE susceptibility gene(s) to be telomeric to the marker D4S2928 by haplotype construction. In addition, marker D4S394 showed marginal evidence of linkage disequilibrium with the putative disease locus by the transmission disequilibrium test and significant evidence of association using a family-based association approach as implemented in the program ASSOC. We also performed both two-point and multipoint model-based analyses to characterize the genetic model of the potential SLE susceptibility gene(s), and the lod scores both maximized under a recessive model with penetrances of 0.8. Finally, we performed a genome-wide scan of the total 153 EA pedigrees and evaluated the possibility of interaction between linkage signals at 4p16 and other regions in the genome. Fourteen regions on 11 chromosomes (1q24, 1q42, 2p11, 2q32, 3p14.2, 4p16, 5p15, 7p21, 8p22, 10q22, 12p11, 12q24, 14q12, 19q13) showed evidence of linkage, among which, signals at 2p11, 12q24 and 19q13 also showed evidence of interaction with that at 4p16. These results provide important additional information about the SLE linkage effect at 4p16 and offer a unique approach to uncovering susceptibility loci involved in complex human diseases.

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Chao Xing
    • 1
  • Andrea L. Sestak
    • 2
  • Jennifer A. Kelly
    • 2
  • Kim L. Nguyen
    • 2
  • Gail R. Bruner
    • 2
  • John B. Harley
    • 2
    • 3
    • 4
  • Courtney Gray-McGuire
    • 1
  1. 1.Division of Genetic and Molecular Epidemiology, Department of Biostatistics and EpidemiologyCase Western Reserve UniversityClevelandUSA
  2. 2.Arthritis and Immunology ProgramOklahoma Medical Research FoundationOklahoma CityUSA
  3. 3.Department of MedicineUniversity of OklahomaOklahoma CityUSA
  4. 4.US Department of Veteran Affairs Medical CenterOklahoma CityUSA