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Title: Two-dimensional genome-scan identifies novel epistatic loci for essential hypertension.
Authors: Bell, JT
Wallace, C
Dobson, R
Wiltshire, S
Mein, C
Pembroke, J
Brown, M
Clayton, D
Samani, N
Dominiczak, A
Webster, J
Lathrop, GM
Connell, J
Munroe, P
Caulfield, M
Farrall, M
First Published: 15-Apr-2006
Citation: HUM MOL GENET, 2006, 15 (8), pp. 1365-1374
Abstract: It is well established that gene interactions influence common human diseases, but to date linkage studies have been constrained to searching for single genes across the genome. We applied a novel approach to uncover significant gene-gene interactions in a systematic two-dimensional (2D) genome-scan of essential hypertension. The study cohort comprised 2076 affected sib-pairs and 66 affected half-sib-pairs of the British Genetics of HyperTension study. Extensive simulations were used to establish significance thresholds in the context of 2D genome-scans. Our analyses found significant and suggestive evidence for loci on chromosomes 5, 9, 11, 15, 16 and 19, which influence hypertension when gene-gene interactions are taken into account (5q13.1 and 11q22.1, two-locus lod score=5.72; 5q13.1 and 19q12, two-locus lod score=5.35; 9q22.3 and 15q12, two-locus lod score=4.80; 16p12.3 and 16q23.1, two-locus lod score=4.50). For each significant and suggestive pairwise interaction, the two-locus genetic model that best fitted the data was determined. Regions that were not detected using single-locus linkage analysis were identified in the 2D scan as contributing significant epistatic effects. This approach has discovered novel loci for hypertension and offers a unique potential to use existing data to uncover novel regions involved in complex human diseases.
DOI Link: 10.1093/hmg/ddl058
ISSN: 0964-6906
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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