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

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.

Adiponectin and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study.

OBJECTIVE: A recent meta-analysis of 13 prospective studies reported that higher levels of adiponectin were significantly associated with lower risk of type 2 diabetes. Most previous studies, however, were limited in their ability to adjust for appropriate confounding variables. Our objective, therefore, was to study this association after adjustment for directly measured adiposity and insulin sensitivity, expressed as the insulin sensitivity index (S(I)). RESEARCH DESIGN AND METHODS: The study included 1,096 Hispanic and African American participants free of diabetes at baseline (2000-2002) who returned for follow-up after 5 years. S(I) was determined from frequently sampled intravenous glucose tolerance tests with minimal model analysis. Visceral adipose tissue (VAT) area was determined by computed tomography. Diabetes and impaired fasting glucose (IFG) were defined using American Diabetes Association criteria. Multivariate generalized estimating equation logistic regression models were used to account for correlations within families. RESULTS: A total of 82 subjects met criteria for incident diabetes. After adjustment for age, sex, ethnicity, and smoking, adiponectin was significantly inversely associated with diabetes (odds ratio [OR] 0.54 per 1 SD difference [95% CI 0.38-0.76]). The association remained significant after additional adjustment in individual models for BMI, homeostasis model assessment of insulin resistance, or VAT (all P < 0.05). However, adiponectin was no longer associated in separate models adjusted for S(I) or IFG (OR 0.81 [0.56-1.16] and 0.75 [0.53-1.06], respectively). CONCLUSIONS: Adiponectin was inversely associated with incident diabetes after adjustment for conventional anthropometric and metabolic variables or VAT. Adjustment for detailed measures of S(I) attenuated this relationship, however, suggesting that the link between adiponectin and diabetes may operate at least in part through insulin resistance.