title: Association of common genetic variants with diabetes and metabolic syndrome related traits in the Arizona Insulin Resistance registry: a focus on Mexican American families in the Southwest.
abstract: OBJECTIVE
  The increased occurrence of type 2 diabetes and its clinical correlates is a global public health issue, and there are continued efforts to find its genetic determinant across ethnically diverse populations. The aims of this study were to determine the heritability of diabetes and metabolic syndrome phenotypes in the Arizona Insulin Resistance (AIR) registry and to perform an association analysis of common single nucleotide polymorphisms (SNPs) identified by GWAS with these traits. All study participants were Mexican Americans from the AIR registry.
  
  
  METHODS
  Metabolic, anthropometric, demographic and medical history information was obtained on the 667 individuals enrolled in the registry.
  
  
  RESULTS
  The heritability estimates were moderate to high in magnitude and significant, indicating that the AIR registry is well suited for the identification of genetic factors contributing to diabetes and the metabolic syndrome. From the 30 GWAS genes selected (some genes were represented by multiple SNPs), 20 SNPs exhibited associations with one or more of the diabetes related traits with nominal significance (p ≤ 0.05). In addition, 25 SNPs were nominally significantly associated with one or more of the metabolic phenotypes tested (p ≤ 0.05). Most notably, 5 SNPs from 5 genes [body mass index (BMI), hip circumference: rs3751812/FTO; fasting plasma glucose, hemoglobin A1c: rs4607517/GCK; very-low-density lipoprotein: rs10830963/MTNR1B; BMI: rs13266634/SLC30A8, and total cholesterol, low-density lipoprotein: rs7578597/THADA] were significantly associated with obesity, glycemic, and lipid phenotypes when using the multiple testing significance threshold of 0.0015.
  
  
  CONCLUSIONS
  These findings extend previous work on Mexican Americans to suggest that metabolic disease is strongly influenced by genetic background in this high-risk population.
authors: School of Life Sciences, Arizona State University, Tempe, Ariz., USA.
authors: Jacob
authors: J
authors: DeMenna
authors: Sobha
authors: S
authors: Puppala
authors: Geetha
authors: G
authors: Chittoor
authors: Jennifer
authors: J
authors: Schneider
authors: Joon Young
authors: JY
authors: Kim
authors: Gabriel Q
authors: GQ
authors: Shaibi
authors: Lawrence J
authors: LJ
authors: Mandarino
authors: Ravindranath
authors: R
authors: Duggirala
authors: Dawn K
authors: DK
authors: Coletta
mesh_terms: D000293:Adolescent; D000328:Adult; D001130:Arizona; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods* / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium; D008055:Lipids / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000208:ethnology / Q000235:genetics*; D017058:Mexican Americans / Q000235:genetics / Q000706:statistics & numerical data; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012042:Registries / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D008055:Lipids