Human Genetics

, Volume 120, Issue 6, pp 807–819

Admixture in Mexico City: implications for admixture mapping of Type 2 diabetes genetic risk factors

Authors

  • Veronica L. Martinez-Marignac
    • Department of AnthropologyUniversity of Toronto at Mississauga
  • Adan Valladares
    • Biochemistry Research Unit, Hospital de Especialidades, Centro Médico “Siglo XXI” Instituto Mexicano del Seguro Social
  • Emily Cameron
    • Department of AnthropologyUniversity of Toronto at Mississauga
  • Andrea Chan
    • Department of AnthropologyUniversity of Toronto at Mississauga
  • Arjuna Perera
    • Department of AnthropologyUniversity of Toronto at Mississauga
  • Rachel Globus-Goldberg
    • Department of AnthropologyUniversity of Toronto at Mississauga
  • Niels Wacher
    • Clinical Epidemiology Research Unit, Hospital de Especialidades, Centro Médico “Siglo XXI” Instituto Mexicano del Seguro Social
  • Jesús Kumate
    • Fundación IMSS
  • Paul McKeigue
    • Conway InstituteUniversity College Dublin
  • David O’Donnell
    • Conway InstituteUniversity College Dublin
  • Mark D. Shriver
    • Department of AnthropologyPenn State University
  • Miguel Cruz
    • Biochemistry Research Unit, Hospital de Especialidades, Centro Médico “Siglo XXI” Instituto Mexicano del Seguro Social
    • Department of AnthropologyUniversity of Toronto at Mississauga
Original Investigation

DOI: 10.1007/s00439-006-0273-3

Cite this article as:
Martinez-Marignac, V.L., Valladares, A., Cameron, E. et al. Hum Genet (2007) 120: 807. doi:10.1007/s00439-006-0273-3

Abstract

Admixture mapping is a recently developed method for identifying genetic risk factors involved in complex traits or diseases showing prevalence differences between major continental groups. Type 2 diabetes (T2D) is at least twice as prevalent in Native American populations as in populations of European ancestry, so admixture mapping is well suited to study the genetic basis of this complex disease. We have characterized the admixture proportions in a sample of 286 unrelated T2D patients and 275 controls from Mexico City and we discuss the implications of the results for admixture mapping studies. Admixture proportions were estimated using 69 autosomal ancestry-informative markers (AIMs). Maternal and paternal contributions were estimated from geographically informative mtDNA and Y-specific polymorphisms. The average proportions of Native American, European and, West African admixture were estimated as 65, 30, and 5%, respectively. The contributions of Native American ancestors to maternal and paternal lineages were estimated as 90 and 40%, respectively. In a logistic model with higher educational status as dependent variable, the odds ratio for higher educational status associated with an increase from 0 to 1 in European admixture proportions was 9.4 (95%, credible interval 3.8–22.6). This association of socioeconomic status with individual admixture proportion shows that genetic stratification in this population is paralleled, and possibly maintained, by socioeconomic stratification. The effective number of generations back to unadmixed ancestors was 6.7 (95% CI 5.7–8.0), from which we can estimate that genome-wide admixture mapping will require typing about 1,400 evenly distributed AIMs to localize genes underlying disease risk between populations of European and Native American ancestry. Sample sizes of about 2,000 cases will be required to detect any locus that contributes an ancestry risk ratio of at least 1.5.

Copyright information

© Springer-Verlag 2006