ePrints

Epistasis between type 2 diabetes susceptibility loci on chromosomes 1q21-25 and 10q23-26 in Northern Europeans

Lookup NU author(s): Professor Mark Walker

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Characterisation of the interactions between susceptibility loci (epistasis) is central to a full understanding of the genetic aetiology and the molecular pathology of complex diseases. We have examined, in British and French pedigrees, evidence for epistasis between the type 2 diabetes susceptibility loci on chromosomes 1q21-25 and 10q23-26 using two complementary linkage-based approaches. Joint two-locus linkage analysis of 1q and 10q in British pedigrees provided significant evidence for interaction (P ≤ 0.003) when comparing a general epistasis model with multiplicative or additive-effects-only models. Conditional linkage analysis (which models epistasis as a deviation from multiplicativity only) confirmed these findings, with significant LOD score increases at the 1q (P = 0.0002) and 10q (P = 0.0023) loci. These analyses provided sizeable reductions in the 1-LOD support intervals for both loci. Analyses of the British and French pedigrees together yielded comparable, but not enhanced, findings, with significant (P ≤ 0.003) evidence for epistasis in joint two-locus linkage analysis, and during conditional linkage analysis significant increases in linkage evidence at the 1q (P = 0.0002) and 10q (P = 0.0036) loci. Our findings of epistasis nevertheless substantiate the evidence for genuine genetic effects at both loci, facilitate endeavours to fine-map these loci in population samples, and support further examination of this interaction at the nucleotide level by providing a robust prior hypothesis. © 2006 The Authors Journal compilation © 2006 University College London.

Publication metadata

Author(s): Wiltshire S, Bell JT, Groves CJ, Dina C, Hattersley AT, Frayling TM, Walker M, Hitman GA, Vaxillaire M, Farrall M, Froguel P, Mccarthy MI

Publication type: Article

Publication status: Published

Journal: Annals of Human Genetics

Year: 2006

Volume: 70

Issue: 6

Pages: 726-737

ISSN (print): 0003-4800

ISSN (electronic): 1469-1809

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1469-1809.2006.00289.x

DOI: 10.1111/j.1469-1809.2006.00289.x

Altmetrics

Share