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01.08.2011 | Article

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas

verfasst von: E. J. Parra, J. E. Below, S. Krithika, A. Valladares, J. L. Barta, N. J. Cox, C. L. Hanis, N. Wacher, J. Garcia-Mena, P. Hu, M. D. Shriver, J. Kumate, P. M. McKeigue, J. Escobedo, M. Cruz, Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium

Erschienen in: Diabetologia | Ausgabe 8/2011

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Abstract

Aims/hypothesis

We report a genome-wide association study of type 2 diabetes in an admixed sample from Mexico City and describe the results of a meta-analysis of this study and another genome-wide scan in a Mexican-American sample from Starr County, TX, USA. The top signals observed in this meta-analysis were followed up in the Diabetes Genetics Replication and Meta-analysis Consortium (DIAGRAM) and DIAGRAM+ datasets.

Methods

We analysed 967 cases and 343 normoglycaemic controls. The samples were genotyped with the Affymetrix Genome-wide Human SNP array 5.0. Associations of genotyped and imputed markers with type 2 diabetes were tested using a missing data likelihood score test. A fixed-effects meta-analysis including 1,804 cases and 780 normoglycaemic controls was carried out by weighting the effect estimates by their inverse variances.

Results

In the meta-analysis of the two Hispanic studies, markers showing suggestive associations (p < 10⁻⁵) were identified in two known diabetes genes, HNF1A and KCNQ1, as well as in several additional regions. Meta-analysis of the two Hispanic studies and the recent DIAGRAM+ dataset identified genome-wide significant signals (p < 5 × 10⁻⁸) within or near the genes HNF1A and CDKN2A/CDKN2B, as well as suggestive associations in three additional regions, IGF2BP2, KCNQ1 and the previously unreported C14orf70.

Conclusions/interpretation

We observed numerous regions with suggestive associations with type 2 diabetes. Some of these signals correspond to regions described in previous studies. However, many of these regions could not be replicated in the DIAGRAM datasets. It is critical to carry out additional studies in Hispanic and American Indian populations, which have a high prevalence of type 2 diabetes.

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Titel: Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas
verfasst von: E. J. Parra
J. E. Below
S. Krithika
A. Valladares
J. L. Barta
N. J. Cox
C. L. Hanis
N. Wacher
J. Garcia-Mena
P. Hu
M. D. Shriver
J. Kumate
P. M. McKeigue
J. Escobedo
M. Cruz
Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium
Publikationsdatum: 01.08.2011
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 8/2011
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-011-2172-y

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