Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans.
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 susceptibili...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2006
|
| _version_ | 1797079249572593664 |
|---|---|
| author | Wiltshire, S Bell, J Groves, C Dina, C Hattersley, A Frayling, T Walker, M Hitman, G Vaxillaire, M Farrall, M Froguel, P McCarthy, M |
| author_facet | Wiltshire, S Bell, J Groves, C Dina, C Hattersley, A Frayling, T Walker, M Hitman, G Vaxillaire, M Farrall, M Froguel, P McCarthy, M |
| author_sort | Wiltshire, S |
| collection | OXFORD |
| description | 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 < or = 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 < or = 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. |
| first_indexed | 2024-03-07T00:43:06Z |
| format | Journal article |
| id | oxford-uuid:83baa2af-9ccc-4817-9a50-ff04daa9dfb0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:43:06Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:83baa2af-9ccc-4817-9a50-ff04daa9dfb02022-03-26T21:46:12ZEpistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:83baa2af-9ccc-4817-9a50-ff04daa9dfb0EnglishSymplectic Elements at Oxford2006Wiltshire, SBell, JGroves, CDina, CHattersley, AFrayling, TWalker, MHitman, GVaxillaire, MFarrall, MFroguel, PMcCarthy, MCharacterisation 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 < or = 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 < or = 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. |
| spellingShingle | Wiltshire, S Bell, J Groves, C Dina, C Hattersley, A Frayling, T Walker, M Hitman, G Vaxillaire, M Farrall, M Froguel, P McCarthy, M Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title | Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title_full | Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title_fullStr | Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title_full_unstemmed | Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title_short | Epistasis between type 2 diabetes susceptibility Loci on chromosomes 1q21-25 and 10q23-26 in northern Europeans. |
| title_sort | epistasis between type 2 diabetes susceptibility loci on chromosomes 1q21 25 and 10q23 26 in northern europeans |
| work_keys_str_mv | AT wiltshires epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT bellj epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT grovesc epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT dinac epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT hattersleya epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT fraylingt epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT walkerm epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT hitmang epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT vaxillairem epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT farrallm epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT froguelp epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans AT mccarthym epistasisbetweentype2diabetessusceptibilitylocionchromosomes1q2125and10q2326innortherneuropeans |