TY - JOUR
T1 - Large-scale association analysis of TNF/LTA gene region polymorphisms in type 2 diabetes
AU - Boraska, Vesna
AU - Rayner, Nigel W.
AU - Groves, Christopher J.
AU - Frayling, Timothy M.
AU - Diakite, Mahamadou
AU - Rockett, Kirk A.
AU - Kwiatkowski, Dominic P.
AU - Day-Williams, Aaron G.
AU - McCarthy, Mark I.
AU - Zeggini, Eleftheria
N1 - Funding Information:
The work was supported by the Diabetes UK RD04/0002809 and RD06/ 0003190 grants. We thank The British Scholarship Trust for support for the VB study visit to Oxford. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk. Fund- ing for the project was provided by the Wellcome Trust under award 076113. This work was supported by the Wellcome Trust (WT088885/Z/09/Z). We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council grant G0000934 and Wellcome Trust grant 068545/Z/02.
PY - 2010/5/6
Y1 - 2010/5/6
N2 - Background: The TNF/LTA locus has been a long-standing T2D candidate gene. Several studies have examined association of TNF/LTA SNPs with T2D but the majority have been small-scale and produced no convincing evidence of association. The purpose of this study is to examine T2D association of tag SNPs in the TNF/LTA region capturing the majority of common variation in a large-scale sample set of UK/Irish origin.Methods: This study comprised a case-control (1520 cases and 2570 control samples) and a family-based component (423 parent-offspring trios). Eleven tag SNPs (rs928815, rs909253, rs746868, rs1041981 (T60N), rs1800750, rs1800629 (G-308A), rs361525 (G-238A), rs3093662, rs3093664, rs3093665, and rs3093668) were selected across the TNF/LTA locus and genotyped using a fluorescence-based competitive allele specific assay. Quality control of the obtained genotypes was performed prior to single- and multi-point association analyses under the additive model.Results: We did not find any consistent SNP associations with T2D in the case-control or family-based datasets.Conclusions: The present study, designed to analyse a set of tag SNPs specifically selected to capture the majority of common variation in the TNF/LTA gene region, found no robust evidence for association with T2D. To investigate the presence of smaller effects of TNF/LTA gene variation with T2D, a large-scale meta-analysis will be required.
AB - Background: The TNF/LTA locus has been a long-standing T2D candidate gene. Several studies have examined association of TNF/LTA SNPs with T2D but the majority have been small-scale and produced no convincing evidence of association. The purpose of this study is to examine T2D association of tag SNPs in the TNF/LTA region capturing the majority of common variation in a large-scale sample set of UK/Irish origin.Methods: This study comprised a case-control (1520 cases and 2570 control samples) and a family-based component (423 parent-offspring trios). Eleven tag SNPs (rs928815, rs909253, rs746868, rs1041981 (T60N), rs1800750, rs1800629 (G-308A), rs361525 (G-238A), rs3093662, rs3093664, rs3093665, and rs3093668) were selected across the TNF/LTA locus and genotyped using a fluorescence-based competitive allele specific assay. Quality control of the obtained genotypes was performed prior to single- and multi-point association analyses under the additive model.Results: We did not find any consistent SNP associations with T2D in the case-control or family-based datasets.Conclusions: The present study, designed to analyse a set of tag SNPs specifically selected to capture the majority of common variation in the TNF/LTA gene region, found no robust evidence for association with T2D. To investigate the presence of smaller effects of TNF/LTA gene variation with T2D, a large-scale meta-analysis will be required.
UR - http://www.scopus.com/inward/record.url?scp=77951819019&partnerID=8YFLogxK
U2 - 10.1186/1471-2350-11-69
DO - 10.1186/1471-2350-11-69
M3 - Article
C2 - 20459604
AN - SCOPUS:77951819019
SN - 1471-2350
VL - 11
JO - BMC Medical Genetics
JF - BMC Medical Genetics
IS - 1
M1 - 69
ER -
