Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes

Cristen J. Willer, Lori L. Bonnycastle, Karen N. Conneely, William L. Duren, Anne U. Jackson, Laura J. Scott, Narisu Narisu, Peter S. Chines, Andrew Skol, Heather M. Stringham, John Petrie, Michael R. Erdos, Amy J. Swift, Sareena T. Enloe, Andrew G. Sprau, Eboni Smith, Maurine Tong, Kimberly F. Doheny, Elizabeth W. Pugh, Richard M. WatanabeThomas A. Buchanan, Timo T. Valle, Richard N. Bergman, Jaakko Tuomilehto, Karen L. Mohlke, Francis S. Collins, Michael Boehnke

Research output: Contribution to journalArticlepeer-review

Abstract

More than 120 published reports have described associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of the same variant have often been discordant. From a literature search, we identified previously reported type 2 diabetes-associated SNPs. We initially genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and 617 control subjects with normal glucose tolerance from Finland and excluded from analysis 20 SNPs in strong linkage disequilibrium (r2 > 0.8) with another typed SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P < 0.10) on an additional 384 case subjects and 366 control subjects from a population-based study in Finland. In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12 SNPs of 114 tested was significantly greater than expected by chance under the null hypothesis of no association (P = 0.012). We observed that SNPs from genes that had three or more previous reports of association were significantly more likely to be replicated in our sample (P = 0.03), although we also replicated 4 of 58 SNPs from genes that had only one previous report of association. 2007

Original languageEnglish (US)
Pages (from-to)256-264
Number of pages9
JournalDiabetes
Volume56
Issue number1
DOIs
StatePublished - Jan 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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