Admixture in Mexico City: implications for admixture mapping of type 2 diabetes genetic risk factors.
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.
Martinez-Marignac
Veronica L
VL
Department of Anthropology, University of Toronto at Mississauga, 3359 Mississauga Rd. Room 4026, South Bldg, L5L 1C6, Mississauga, ON, Canada, eparra@utm.utoronto.ca.
Valladares
Adan
A
Cameron
Emily
E
Chan
Andrea
A
Perera
Arjuna
A
Globus-Goldberg
Rachel
R
Wacher
Niels
N
Kumate
Jesús
J
McKeigue
Paul
P
O'Donnell
David
D
Shriver
Mark D
MD
Cruz
Miguel
M
Parra
Esteban J
EJ
D000354:Africa, Western / Q000208:ethnology; D000483:Alleles; D001483:Base Sequence; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D051456:Gene Flow; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008800:Mexico; D008957:Models, Genetic; D012307:Risk Factors; D044465:White People / Q000235:genetics
D017931:DNA Primers; D004272:DNA, Mitochondrial; D005819:Genetic Markers