We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants¹, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13–1.27), P = 7.7 10^-9) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11–1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31–1.72) and 1.55 (1.23–1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

1. deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
2. Landspitali-University Hospital, 101 Reykjavik, Iceland.
3. Icelandic Heart Association, 201 Kopavogur, Iceland.
4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
5. Steno Diabetes Center, DK-2820 Copenhagen, Denmark.
6. Center for Clinical and Basic Research A/S, DK-2750 Ballerup, Denmark.
7. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
8. National Human Genome Center, Howard University, Department of Community and Family Medicine, Washington, DC 20060, USA.
9. Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.
10. Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
11. Department of Molecular Genetics, Maastricht University, 6200 MD Maastricht, The Netherlands.
12. Department of Pathology and Laboratory Medicine, University Medical Center Groningen (UMCG), 9700 RB Groningen, The Netherlands
13. Department of Genetics, University Medical Center Groningen (UMCG), 9700 RB Groningen, The Netherlands.
14. Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands.
15. These authors contributed equally to this work.

Correspondence to: Kari Stefansson¹ e-mail: kstefans@decode.is

Correspondence to: Valgerdur Steinthorsdottir^1,15 e-mail: vstein@decode.is

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NPG Journals

by Subject Area

• Chemistry

  • Chemistry
  • Drug discovery
  • Biotechnology
  • Materials
  • Methods & Protocols

• Clinical Practice & Research

  • Cancer
  • Cardiovascular medicine
  • Dentistry
  • Endocrinology
  • Gastroenterology & Hepatology
  • Methods & Protocols
  • Pathology & Pathobiology
  • Urology

• Earth & Environment

  • Earth sciences
  • Evolution & Ecology

• Life sciences

  • Biotechnology
  • Cancer
  • Development
  • Drug discovery
  • Evolution & Ecology
  • Genetics
  • Immunology
  • Medical research
  • Methods & Protocols
  • Microbiology
  • Molecular cell biology
  • Neuroscience
  • Pharmacology
  • Systems biology

• Physical sciences

  • Physics
  • Materials

by A - Z Index