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Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans

Author

Listed:
  • Jacob M Keaton
  • Jacklyn N Hellwege
  • Maggie C Y Ng
  • Nicholette D Palmer
  • James S Pankow
  • Myriam Fornage
  • James G Wilson
  • Adolfo Correa
  • Laura J Rasmussen-Torvik
  • Jerome I Rotter
  • Yii-Der I Chen
  • Kent D Taylor
  • Stephen S Rich
  • Lynne E Wagenknecht
  • Barry I Freedman
  • Donald W Bowden

Abstract

Type 2 diabetes (T2D) is the result of metabolic defects in insulin secretion and insulin sensitivity, yet most T2D loci identified to date influence insulin secretion. We hypothesized that T2D loci, particularly those affecting insulin sensitivity, can be identified through interaction with insulin secretion loci. To test this hypothesis, single nucleotide polymorphisms (SNPs) associated with acute insulin response to glucose (AIRg), a dynamic measure of first-phase insulin secretion, were identified in African Americans from the Insulin Resistance Atherosclerosis Family Study (IRASFS; n = 492 subjects). These SNPs were tested for interaction, individually and jointly as a genetic risk score (GRS), using genome-wide association study (GWAS) data from five cohorts (ARIC, CARDIA, JHS, MESA, WFSM; n = 2,725 cases, 4,167 controls) with T2D as the outcome. In single variant analyses, suggestively significant (Pinteraction

Suggested Citation

  • Jacob M Keaton & Jacklyn N Hellwege & Maggie C Y Ng & Nicholette D Palmer & James S Pankow & Myriam Fornage & James G Wilson & Adolfo Correa & Laura J Rasmussen-Torvik & Jerome I Rotter & Yii-Der I Ch, 2016. "Genome-Wide Interaction with Insulin Secretion Loci Reveals Novel Loci for Type 2 Diabetes in African Americans," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-12, July.
    • Handle: RePEc:plo:pone00:0159977
    DOI: 10.1371/journal.pone.0159977
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    References listed on IDEAS

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    2. Mayumi Inoue & Louise Chang & Joseph Hwang & Shian-Huey Chiang & Alan R. Saltiel, 2003. "The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin," Nature, Nature, vol. 422(6932), pages 629-633, April.
    3. Nicholette D Palmer & Caitrin W McDonough & Pamela J Hicks & Bong H Roh & Maria R Wing & S Sandy An & Jessica M Hester & Jessica N Cooke & Meredith A Bostrom & Megan E Rudock & Matthew E Talbert & Jos, 2012. "A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-14, January.
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