Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study

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  • Franceschini, Nora
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Almasy, Laura
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • MacCluer, Jean W
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • Göring, Harald HH
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • Cole, Shelley A
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • Diego, Vincent P
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • Laston, Sandra
    • Other Affiliation: Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA
  • Howard, Barbara V
    • Other Affiliation: MedStar Research Institute, Washington, DC, USA
  • Lee, Elisa T
    • Other Affiliation: Center for American Indian Health Research, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
  • Best, Lyle G
    • Other Affiliation: Missouri Breaks Industries Research, Inc., Timber Lake, SD, USA
  • Fabsitz, Richard R
    • Other Affiliation: Epidemiology and Biometry Program, National Heart, Lung and Blood Institute, Bethesda, MD, USA
  • North, Kari
    • Affiliation: School of Medicine, Carolina Center for Genome Sciences
Abstract
  • Abstract Background Body fat mass distribution and deposition are determined by multiple environmental and genetic factors. Obesity is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes. We previously identified evidence for genotype-by-diabetes interaction on obesity traits in Strong Heart Family Study (SHFS) participants. To localize these genetic effects, we conducted genome-wide linkage scans of obesity traits in individuals with and without type 2 diabetes, and in the combined sample while modeling interaction with diabetes using maximum likelihood methods (SOLAR 2.1.4). Methods SHFS recruited American Indians from Arizona, North and South Dakota, and Oklahoma. Anthropometric measures and diabetes status were obtained during a clinic visit. Marker allele frequencies were derived using maximum likelihood methods estimated from all individuals and multipoint identity by descent sharing was estimated using Loki. We used variance component linkage analysis to localize quantitative trait loci (QTLs) influencing obesity traits. We tested for evidence of additive and QTL-specific genotype-by-diabetes interactions using the regions identified in the diabetes-stratified analyses. Results Among 245 diabetic and 704 non-diabetic American Indian individuals, we detected significant additive gene-by-diabetes interaction for weight and BMI (P < 0.02). In analysis accounting for QTL-specific interaction (P < 0.001), we detected a QTL for weight on chromosome 1 at 242 cM (LOD = 3.7). This chromosome region harbors the adiponectin receptor 1 gene, which has been previously associated with obesity. Conclusion These results suggest distinct genetic effects on body mass in individuals with diabetes compared to those without diabetes, and a possible role for one or more genes on chromosome 1 in the pathogenesis of obesity.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Nora Franceschini et al.; licensee BioMed Central Ltd.
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Journal title
  • BMC Medical Genetics
Journal volume
  • 9
Journal issue
  • 1
Page start
  • 90
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1471-2350
Bibliographic citation
  • BMC Medical Genetics. 2008 Oct 14;9(1):90
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • July 16, 2016

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