Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA)

Laura J. Rasmussen-Torvik, Xiuqing Guo, Donald W. Bowden, Alain G. Bertoni, Michele M. Sale, Jie Yao, David A. Bluemke, Mark O. Goodarzi, Y. Ida Chen, Dhananjay Vaidya, Leslie J. Raffel, George J. Papanicolaou, James B. Meigs, James S. Pankow

Research output: Contribution to journalArticle

Abstract

Genetic variants associated with fasting glucose in European ancestry populations are increasingly well understood. However, the nature of the associations between these single nucleotide polymorphisms (SNPs) and fasting glucose in other racial and ethnic groups is unclear. We sought to examine regions previously identified to be associated with fasting glucose in Caucasian genome-wide association studies (GWAS) across multiple ethnicities in the Multiethnic Study of Atherosclerosis (MESA). Nondiabetic MESA participants with fasting glucose measured at the baseline exam and with GWAS genotyping were included; 2,349 Caucasians, 664 individuals of Chinese descent, 1,366 African Americans, and 1,171 Hispanics. Genotype data were generated from the Affymetrix 6.0 array and imputation in IMPUTE. Fasting glucose was regressed on SNP dosage data in each ethnic group adjusting for age, gender, MESA study center, and ethnic-specific principal components. SNPs from the three gene regions with the strongest associations to fasting glucose in previous Caucasian GWAS (MTNR1B / GCK / G6PC2) were examined in depth. There was limited power to replicate associations in other ethnic groups due to smaller allele frequencies and limited sample size; SNP associations may also have differed across ethnic groups due to differing linkage disequilibrium patterns with causal variants. rs10830963 in MTNR1B and rs4607517 in GCK demonstrated consistent magnitude and direction of association with fasting glucose across ethnic groups, although the associations were often not nominally significant. In conclusion, certain SNPs in MTNR1B and GCK demonstrate consistent effects across four racial and ethnic groups, narrowing the putative region for these causal variants.

Original languageEnglish (US)
Pages (from-to)384-391
Number of pages8
JournalGenetic Epidemiology
Volume36
Issue number4
DOIs
StatePublished - May 2012

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Genome-Wide Association Study
Ethnic Groups
Fasting
Atherosclerosis
Glucose
Single Nucleotide Polymorphism
Linkage Disequilibrium
Hispanic Americans
Gene Frequency
African Americans
Sample Size
Genotype
Population
Genes

Keywords

  • Fasting glucose
  • GWAS
  • SNP

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Rasmussen-Torvik, L. J., Guo, X., Bowden, D. W., Bertoni, A. G., Sale, M. M., Yao, J., ... Pankow, J. S. (2012). Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). Genetic Epidemiology, 36(4), 384-391. https://doi.org/10.1002/gepi.21632

Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). / Rasmussen-Torvik, Laura J.; Guo, Xiuqing; Bowden, Donald W.; Bertoni, Alain G.; Sale, Michele M.; Yao, Jie; Bluemke, David A.; Goodarzi, Mark O.; Chen, Y. Ida; Vaidya, Dhananjay; Raffel, Leslie J.; Papanicolaou, George J.; Meigs, James B.; Pankow, James S.

In: Genetic Epidemiology, Vol. 36, No. 4, 05.2012, p. 384-391.

Research output: Contribution to journalArticle

Rasmussen-Torvik, LJ, Guo, X, Bowden, DW, Bertoni, AG, Sale, MM, Yao, J, Bluemke, DA, Goodarzi, MO, Chen, YI, Vaidya, D, Raffel, LJ, Papanicolaou, GJ, Meigs, JB & Pankow, JS 2012, 'Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA)', Genetic Epidemiology, vol. 36, no. 4, pp. 384-391. https://doi.org/10.1002/gepi.21632
Rasmussen-Torvik, Laura J. ; Guo, Xiuqing ; Bowden, Donald W. ; Bertoni, Alain G. ; Sale, Michele M. ; Yao, Jie ; Bluemke, David A. ; Goodarzi, Mark O. ; Chen, Y. Ida ; Vaidya, Dhananjay ; Raffel, Leslie J. ; Papanicolaou, George J. ; Meigs, James B. ; Pankow, James S. / Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). In: Genetic Epidemiology. 2012 ; Vol. 36, No. 4. pp. 384-391.
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AU - Vaidya, Dhananjay

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