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

Jacob DeMenna, Sobha Puppala, Geetha Chittoor, Jennifer Schneider, Joon Young Kim, Gabriel Shaibi, Lawrence J. Mandarino, Ravindranath Duggirala, Dawn K. Coletta

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background/Aims: 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. Conclusion: These findings extend previous work on Mexican Americans to suggest that metabolic disease is strongly influenced by genetic background in this high-risk population.

Original languageEnglish (US)
Pages (from-to)47-58
Number of pages12
JournalHuman Heredity
Volume78
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Single Nucleotide Polymorphism
Registries
Insulin Resistance
Genome-Wide Association Study
Phenotype
Body Mass Index
Genes
VLDL Lipoproteins
Metabolic Diseases
LDL Cholesterol
Type 2 Diabetes Mellitus
Population
Hip
Fasting
Hemoglobins
Public Health
Obesity
Demography
Lipids
Glucose

Keywords

  • Arizona Insulin Resistance registry
  • Diabetes
  • GWAS
  • Metabolic syndrome
  • Mexican Americans
  • SNP genotyping

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)

Cite this

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. / DeMenna, Jacob; Puppala, Sobha; Chittoor, Geetha; Schneider, Jennifer; Kim, Joon Young; Shaibi, Gabriel; Mandarino, Lawrence J.; Duggirala, Ravindranath; Coletta, Dawn K.

In: Human Heredity, Vol. 78, No. 1, 2014, p. 47-58.

Research output: Contribution to journalArticle

DeMenna, Jacob ; Puppala, Sobha ; Chittoor, Geetha ; Schneider, Jennifer ; Kim, Joon Young ; Shaibi, Gabriel ; Mandarino, Lawrence J. ; Duggirala, Ravindranath ; Coletta, Dawn K. / 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. In: Human Heredity. 2014 ; Vol. 78, No. 1. pp. 47-58.
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abstract = "Background/Aims: 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. Conclusion: These findings extend previous work on Mexican Americans to suggest that metabolic disease is strongly influenced by genetic background in this high-risk population.",
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AU - Schneider, Jennifer

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