Polymorphisms in <Emphasis Type="Italic">AHI1</Emphasis> are not associated with type 2 diabetes or related phenotypes in Danes: non-replication of a genome-wide association result |
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Authors: | J Holmkvist S Anthonsen L Wegner G Andersen T Jørgensen K Borch-Johnsen A Sandbæk T Lauritzen O Pedersen T Hansen |
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Institution: | (1) Steno Diabetes Center, Niels Steensens Vej 1, NLC2.12, 2820 Gentofte, Denmark;(2) Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark;(3) Faculty of Health Science, University of Aarhus, Aarhus, Denmark;(4) Department of General Practice, University of Aarhus, Aarhus, Denmark |
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Abstract: | Aims/hypothesis A genome-wide association study recently identified an association between common variants, rs1535435 and rs9494266, in the
AHI1 gene and type 2 diabetes. The aim of the present study was to investigate the putative association between these polymorphisms
and type 2 diabetes or type 2 diabetes-related metabolic traits in Danish individuals.
Methods The previously associated polymorphisms were genotyped in the population-based Inter99 cohort (n = 6162), the Danish ADDITION study (n = 8428), a population-based sample of young healthy participants (n = 377) and in additional type 2 diabetes (n = 2107) and glucose-tolerant participants (n = 483) using Taqman allelic discrimination. The case–control study involved 4,104 type 2 diabetic patients and 5,050 glucose-tolerant
control participants. Type 2 diabetes-related traits were investigated in 17,521 individuals.
Results rs1535435 and rs9494266 were not associated with type 2 diabetes. Odds ratios (OR) were ORadd 1.0 (95% C.I. 0.9–1.2; p
add = 0.7) and ORadd 1.1 (0.9–1.2; p
add = 0.4), respectively, a finding supported by meta-analyses: ORadd 1.0 (0.9–1.1; p
add = 0.6) and ORadd 1.0 (0.9–1.1; p
add = 0.6), respectively. Neither rs1535435 nor rs9494266 were consistently associated with any of the tested type 2 diabetes-related
metabolic traits.
Conclusions/interpretation Data from large samples of Danish individuals do not support a role for AHI1 rs1535435 nor rs9494266 as major type 2 diabetes variants. This study highlights the importance of independent and well-powered
replication studies of the recent genome-wide association scans before a locus is robustly validated as being associated with
type 2 diabetes.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. |
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Keywords: | AHI1 Association Chromosome 6 Genetics Single nucleotide polymorphism SNP Type 2 diabetes |
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