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Identification of Allelic Heterogeneity at Type-2 Diabetes Loci and Impact on Prediction

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  • Yann C Klimentidis
  • Jin Zhou
  • Nathan E Wineinger

Abstract

Although over 60 single nucleotide polymorphisms (SNPs) have been identified by meta-analysis of genome-wide association studies for type-2 diabetes (T2D) among individuals of European descent, much of the genetic variation remains unexplained. There are likely many more SNPs that contribute to variation in T2D risk, some of which may lie in the regions surrounding established SNPs - a phenomenon often referred to as allelic heterogeneity. Here, we use the summary statistics from the DIAGRAM consortium meta-analysis of T2D genome-wide association studies along with linkage disequilibrium patterns inferred from a large reference sample to identify novel SNPs associated with T2D surrounding each of the previously established risk loci. We then examine the extent to which the use of these additional SNPs improves prediction of T2D risk in an independent validation dataset. Our results suggest that multiple SNPs at each of 3 loci contribute to T2D susceptibility (TCF7L2, CDKN2A/B, and KCNQ1; p

Suggested Citation

  • Yann C Klimentidis & Jin Zhou & Nathan E Wineinger, 2014. "Identification of Allelic Heterogeneity at Type-2 Diabetes Loci and Impact on Prediction," PLOS ONE, Public Library of Science, vol. 9(11), pages 1-7, November.
    • Handle: RePEc:plo:pone00:0113072
    DOI: 10.1371/journal.pone.0113072
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    1. Xueling Sim & Rick Twee-Hee Ong & Chen Suo & Wan-Ting Tay & Jianjun Liu & Daniel Peng-Keat Ng & Michael Boehnke & Kee-Seng Chia & Tien-Yin Wong & Mark Seielstad & Yik-Ying Teo & E-Shyong Tai, 2011. "Transferability of Type 2 Diabetes Implicated Loci in Multi-Ethnic Cohorts from Southeast Asia," PLOS Genetics, Public Library of Science, vol. 7(4), pages 1-12, April.
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    1. Magdalena Marcińska & Ewelina Pośpiech & Sarah Abidi & Jeppe Dyrberg Andersen & Margreet van den Berge & Ángel Carracedo & Mayra Eduardoff & Anna Marczakiewicz-Lustig & Niels Morling & Titia Sijen & M, 2015. "Evaluation of DNA Variants Associated with Androgenetic Alopecia and Their Potential to Predict Male Pattern Baldness," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-18, May.

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