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

Diabet Genetics Replication Meta-A; 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

doi:10.1007/s00125-011-2172-y

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

Diabet Genetics Replication Meta-A, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

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.

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 x 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.

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.

Original language	English
Pages (from-to)	2038-2046
Number of pages	9
Journal	Diabetologia
Volume	54
Issue number	8
DOIs	https://doi.org/10.1007/s00125-011-2172-y
Publication status	Published - 15 May 2011

Keywords / Materials (for Non-textual outputs)

GENES
RISK LOCI
POPULATIONS
SUSCEPTIBILITY LOCI
Meta-analysis
Genome-wide association
Type 2 diabetes
KCNQ1
VARIANTS
ADMIXTURE
Hispanics
REPLICATION

Access to Document

10.1007/s00125-011-2172-y

Cite this

Diabet Genetics Replication Meta-A, Parra, E. J., Below, J. E., Krithika, S., Valladares, A., Barta, J. L., Cox, N. J., Hanis, C. L., Wacher, N., Garcia-Mena, J., Hu, P., Shriver, M. D., Kumate, J., McKeigue, P. M., Escobedo, J., & Cruz, M. (2011). 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. Diabetologia, 54(8), 2038-2046. https://doi.org/10.1007/s00125-011-2172-y

@article{3bbfa08abb5f43f8903182f1eb8e8b8a,

title = "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",

abstract = "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.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.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 x 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.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.",

keywords = "GENES, RISK LOCI, POPULATIONS, SUSCEPTIBILITY LOCI, Meta-analysis, Genome-wide association, Type 2 diabetes, KCNQ1, VARIANTS, ADMIXTURE, Hispanics, REPLICATION",

author = "{Diabet Genetics Replication Meta-A} and Parra, {E. J.} and Below, {J. E.} and S. Krithika and A. Valladares and Barta, {J. L.} and Cox, {N. J.} and Hanis, {C. L.} and N. Wacher and J. Garcia-Mena and P. Hu and Shriver, {M. D.} and J. Kumate and McKeigue, {P. M.} and J. Escobedo and M. Cruz",

year = "2011",

month = may,

day = "15",

doi = "10.1007/s00125-011-2172-y",

language = "English",

volume = "54",

pages = "2038--2046",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer",

number = "8",

}

Diabet Genetics Replication Meta-A, Parra, EJ, Below, JE, Krithika, S, Valladares, A, Barta, JL, Cox, NJ, Hanis, CL, Wacher, N, Garcia-Mena, J, Hu, P, Shriver, MD, Kumate, J, McKeigue, PM, Escobedo, J & Cruz, M 2011, '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', Diabetologia, vol. 54, no. 8, pp. 2038-2046. https://doi.org/10.1007/s00125-011-2172-y

TY - JOUR

T1 - 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

AU - Diabet Genetics Replication Meta-A

AU - Parra, E. J.

AU - Below, J. E.

AU - Krithika, S.

AU - Valladares, A.

AU - Barta, J. L.

AU - Cox, N. J.

AU - Hanis, C. L.

AU - Wacher, N.

AU - Garcia-Mena, J.

AU - Hu, P.

AU - Shriver, M. D.

AU - Kumate, J.

AU - McKeigue, P. M.

AU - Escobedo, J.

AU - Cruz, M.

PY - 2011/5/15

Y1 - 2011/5/15

N2 - 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.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.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 x 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.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.

AB - 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.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.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 x 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.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.

KW - GENES

KW - RISK LOCI

KW - POPULATIONS

KW - SUSCEPTIBILITY LOCI

KW - Meta-analysis

KW - Genome-wide association

KW - Type 2 diabetes

KW - KCNQ1

KW - VARIANTS

KW - ADMIXTURE

KW - Hispanics

KW - REPLICATION

U2 - 10.1007/s00125-011-2172-y

DO - 10.1007/s00125-011-2172-y

M3 - Article

SN - 0012-186X

VL - 54

SP - 2038

EP - 2046

JO - Diabetologia

JF - Diabetologia

IS - 8

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Cite this