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Fine-scale linkage disequilibrium mapping of age-related macular degeneration in the complement factor H gene region

Fine-scale linkage disequilibrium mapping of age-related macular degeneration in the complement factor H gene region
Fine-scale linkage disequilibrium mapping of age-related macular degeneration in the complement factor H gene region
Aim: To present results from a nested association study of the complement factor H (CFH) gene region using a novel methodology that uses a high-resolution genetic linkage disequilibrium map to estimate a point location for a causal mutation.

Method: Age-related macular degeneration (AMD) case–control data from a genomewide single-nucleotide polymorphism (SNP) panel were used to identify the target interval to be genotyped at higher density in a second independent panel. The pattern of linkage disequilibrium (LD) and segmental duplications across this region are described in detail.

Result: Data were consistent with other studies in that strong association between the Y402H variant and AMD is observed. However, composite likelihood analysis, which combines association data from all SNPs in the region, and uses genetic locations on a high-resolution LD map, gave a point location for a causal variant between exons 1 and 2 of the CFH gene.

Conclusion: The findings are consistent with evidence that, in addition to the widely described Y402H variant, there is at least one and, most probably, several other mutations in the CFH gene which determine disease manifestation in AMD. A genetic model in which multiple mutations contribute to a varying degree to disease aetiology has been previously well described in ophthalmic genetics, and is typified by the COL2A1 and ABCA4 genes.
epidemiology, mutation, linkage disequilibrium, single nucleotide, aged, genetic predisposition to disease, complement factor h, genes, chromosomes, humans, human, macular degeneration, disease, research, analysis, research support, pair 1, exons, genotype, polymorphism, middle aged, case-control studies, genetics, cfh, association, eye, model, haplotype, mutations, map, susceptibility, strong association, hemochromatosis, human genome, y402h variant, amd, variant, gene, dna
0007-1161
966-970
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Goverdhan, Srini
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Hoh, Josephine
d26bda13-f357-4bfd-b8a8-8377a50ee8a5
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Ennis, Sarah
7b57f188-9d91-4beb-b217-09856146f1e9
Goverdhan, Srini
9ae32d5a-5c82-48a4-962d-1ed8acc3991e
Cree, Angela
6724b71b-8828-4abb-971f-0856c2af555e
Hoh, Josephine
d26bda13-f357-4bfd-b8a8-8377a50ee8a5
Collins, Andrew
7daa83eb-0b21-43b2-af1a-e38fb36e2a64
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Ennis, Sarah, Goverdhan, Srini, Cree, Angela, Hoh, Josephine, Collins, Andrew and Lotery, Andrew (2007) Fine-scale linkage disequilibrium mapping of age-related macular degeneration in the complement factor H gene region. British Journal of Ophthalmology, 91 (7), 966-970. (doi:10.1136/bjo.2007.114090).

Record type: Article

Abstract

Aim: To present results from a nested association study of the complement factor H (CFH) gene region using a novel methodology that uses a high-resolution genetic linkage disequilibrium map to estimate a point location for a causal mutation.

Method: Age-related macular degeneration (AMD) case–control data from a genomewide single-nucleotide polymorphism (SNP) panel were used to identify the target interval to be genotyped at higher density in a second independent panel. The pattern of linkage disequilibrium (LD) and segmental duplications across this region are described in detail.

Result: Data were consistent with other studies in that strong association between the Y402H variant and AMD is observed. However, composite likelihood analysis, which combines association data from all SNPs in the region, and uses genetic locations on a high-resolution LD map, gave a point location for a causal variant between exons 1 and 2 of the CFH gene.

Conclusion: The findings are consistent with evidence that, in addition to the widely described Y402H variant, there is at least one and, most probably, several other mutations in the CFH gene which determine disease manifestation in AMD. A genetic model in which multiple mutations contribute to a varying degree to disease aetiology has been previously well described in ophthalmic genetics, and is typified by the COL2A1 and ABCA4 genes.

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Published date: July 2007
Additional Information: Extended report
Keywords: epidemiology, mutation, linkage disequilibrium, single nucleotide, aged, genetic predisposition to disease, complement factor h, genes, chromosomes, humans, human, macular degeneration, disease, research, analysis, research support, pair 1, exons, genotype, polymorphism, middle aged, case-control studies, genetics, cfh, association, eye, model, haplotype, mutations, map, susceptibility, strong association, hemochromatosis, human genome, y402h variant, amd, variant, gene, dna
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 47964
URI: http://eprints.soton.ac.uk/id/eprint/47964
ISSN: 0007-1161
PURE UUID: 92a1258f-71d4-4955-be6b-c94d61a1b2ec
ORCID for Sarah Ennis: ORCID iD orcid.org/0000-0003-2648-0869
ORCID for Andrew Collins: ORCID iD orcid.org/0000-0001-7108-0771
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 16 Aug 2007
Last modified: 07 Oct 2020 01:48

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