TY - JOUR
T1 - Admixture in Mexico City
T2 - Implications for admixture mapping of Type 2 diabetes genetic risk factors
AU - Martinez-Marignac, Veronica L.
AU - Valladares, Adan
AU - Cameron, Emily
AU - Chan, Andrea
AU - Perera, Arjuna
AU - Globus-Goldberg, Rachel
AU - Wacher, Niels
AU - Kumate, Jesús
AU - McKeigue, Paul
AU - O'Donnell, David
AU - Shriver, Mark D.
AU - Cruz, Miguel
AU - Parra, Esteban J.
N1 - Funding Information:
Acknowledgments We would like to thank all the individuals from Mexico City for their participation in this study. We are also grateful to the personnel at the National Blood Bank, Medical Center Siglo XXI (IMSS) in Mexico. This work was supported by the Fondo para el Fomento de Investigacion (FOFOI) and the Instituto Mexicano del Seguro Social (IMSS)
Funding Information:
in Mexico. EJP was supported by the Banting and Best Diabetes Centre at the University of Toronto, The Canada Foundation for Innovation (CFI), The Ontario Innovation Trust (OIT) and the Canadian Institutes of Health Research (CIHR). MDS, DO, and PM are supported by a grant from the NIH/NHGRI (HG02154). Finally, we would like to thank David Ramos, Alfonso Alcantara, and Olga Gaja for their excellent technical support
PY - 2007/1
Y1 - 2007/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-006-0273-3
DO - 10.1007/s00439-006-0273-3
M3 - Article
C2 - 17066296
AN - SCOPUS:33846351248
SN - 0340-6717
VL - 120
SP - 807
EP - 819
JO - Human genetics
JF - Human genetics
IS - 6
ER -
