Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium - PubMed (original) (raw)

doi: 10.1086/520599. Epub 2007 Jun 26.

Pekka Uimari, Juha-Matti Aalto, Mia Pirskanen, Jari Kaikkonen, Boryana Todorova, Jelena Hyppönen, Veli-Pekka Korhonen, Janne Asikainen, Christopher Devine, Tomi-Pekka Tuomainen, Jan Luedemann, Matthias Nauck, Wolfgang Kerner, Richard H Stephens, John P New, William E Ollier, J Martin Gibson, Antony Payton, Michael A Horan, Neil Pendleton, Walt Mahoney, David Meyre, Jerôme Delplanque, Philippe Froguel, Oren Luzzatto, Benjamin Yakir, Ariel Darvasi

Affiliations

Type 2 diabetes whole-genome association study in four populations: the DiaGen consortium

Jukka T Salonen et al. Am J Hum Genet. 2007 Aug.

Abstract

Type 2 diabetes (T2D) is a common, polygenic chronic disease with high heritability. The purpose of this whole-genome association study was to discover novel T2D-associated genes. We genotyped 500 familial cases and 497 controls with >300,000 HapMap-derived tagging single-nucleotide-polymorphism (SNP) markers. When a stringent statistical correction for multiple testing was used, the only significant SNP was at TCF7L2, which has already been discovered and confirmed as a T2D-susceptibility gene. For a replication study, we selected 10 SNPs in six chromosomal regions with the strongest association (singly or as part of a haplotype) for retesting in an independent case-control set including 2,573 T2D cases and 2,776 controls. The most significant replicated result was found at the AHI1-LOC441171 gene region.

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Figures

Figure 1.

Figure 1.

Distribution of MAFs in 317,503 SNPs

Figure 2.

Figure 2.

Vertical lines plotted for each SNP analyzed, placed according to their chromosomal locations. The height of the lines correspond to the nominal P value (plotted as −log_P_) of each SNP as obtained from a single-point analysis with use of a Cochran-Mantel-Haenszel χ2 test (see the “Material and Methods” section). The horizontal dashed lines (at

-_logP_=6.64

,

_P_=2.3×10-7

) correspond to the statistical threshold adjusted for multiple testing and an overall statistical significance of .05, after 1,000 permutations.

Figure 3.

Figure 3.

Pairwise LD diagram for SNPs in the AHI1 gene region. The LD between pairs of SNPs is presented using _D_′, which was calculated from the DiaGen genotyping data with Haploview software. The bar graph indicates the negative logarithm of the P value for each SNP from single-point analysis.

References

Web Resources

    1. HapMap Project and SNP Consortium, http://www.hapmap.org/
    1. Human Genome Project, http://www.ornl.gov/sci/techresources/Human_Genome/home.shtml
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for T2D, TCF7L2, PPARγ, KCNJ11, CAPN10, AHI1, MYO10, and obesity)
    1. The R Project for Statistical Computing, http://www.r-project.org/ - PubMed

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