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Abstract / Description of output
Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)–HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10−72), CFH (complement factor H) (P =2.3 × 10−47), C2 (complement component 2)–CFB (complement factor B) (P =5.2 × 10−9), C3 (complement component 3) (P =2.2 × 10−3) and CFI (P =3.6 × 10−3) and with more recently reported risk loci at VEGFA (P =1.2 × 10−3) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)–FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10−7, replication P =3.0 × 10−4, combined P =1.3 × 10−9, odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3–1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10−8, replication P =3.8 × 10−5, combined P =2.0 × 10−11, OR = 1.3, 95% CI = 1.2–1.4). These associations remained significant in conditional analyses which included the adjacent C2–CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.
Original language | English |
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Pages (from-to) | 4138-4150 |
Number of pages | 13 |
Journal | Human Molecular Genetics |
Volume | 21 |
Issue number | 18 |
DOIs | |
Publication status | Published - 15 Sept 2012 |
Keywords / Materials (for Non-textual outputs)
- GENES
- RISK
- COMPONENT 2
- COMPLEMENT FACTOR-H
- SUSCEPTIBILITY
- POLYMORPHISM
- FACTOR-B
- ANGIOGENESIS
- TENASCIN-X
- ENDOTHELIAL GROWTH-FACTOR
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A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I., Bates, T., Gow, A. & Starr, J.
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research
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Testing the common cause hypothesis of cognitive ageing in the Lothian birth cohort 1921
Deary, I., Bates, T., Gow, A. & Starr, J.
UK central government bodies/local authorities, health and hospital authorities
1/06/07 → 31/05/09
Project: Research