Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0025598
Title: A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration
Authors: Sivakumaran, T.A.
Igo Jr., R.P.
Kidd, J.M.
Itsara, A.
Kopplin, L.J.
Chen, W.
Hagstrom, S.A.
Peachey, N.S.
Francis, P.J.
Klein, M.L.
Chew, E.Y.
Ramprasad, V.L.
Tay, W.-T.
Mitchell, P.
Seielstad, M.
Stambolian, D.E.
Edwards, A.O.
Lee, K.E.
Leontiev, D.V.
Jun, G.
Wang, Y.
Tian, L.
Qiu, F.
Henning, A.K.
LaFramboise, T.
Sen, P.
Aarthi, M.
George, R.
Raman, R.
Das, M.K.
Vijaya, L.
Kumaramanickavel, G.
Wong, T.Y. 
Swaroop, A.
Abecasis, G.R.
Klein, R.
Klein, B.E.K.
Nickerson, D.A.
Eichler, E.E.
Iyengar, S.K.
Issue Date: 12-Oct-2011
Citation: Sivakumaran, T.A., Igo Jr., R.P., Kidd, J.M., Itsara, A., Kopplin, L.J., Chen, W., Hagstrom, S.A., Peachey, N.S., Francis, P.J., Klein, M.L., Chew, E.Y., Ramprasad, V.L., Tay, W.-T., Mitchell, P., Seielstad, M., Stambolian, D.E., Edwards, A.O., Lee, K.E., Leontiev, D.V., Jun, G., Wang, Y., Tian, L., Qiu, F., Henning, A.K., LaFramboise, T., Sen, P., Aarthi, M., George, R., Raman, R., Das, M.K., Vijaya, L., Kumaramanickavel, G., Wong, T.Y., Swaroop, A., Abecasis, G.R., Klein, R., Klein, B.E.K., Nickerson, D.A., Eichler, E.E., Iyengar, S.K. (2011-10-12). A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration. PLoS ONE 6 (10) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0025598
Abstract: Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N= 293) and AMD cases (White N= 4210 Indian= 134; Malay= 140) and controls (White N= 3229; Indian= 117; Malay= 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p= 8.31×10 -109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10 -9) and by 15.57-fold (P= 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number. © 2011 Sivakumaran et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/109135
ISSN: 19326203
DOI: 10.1371/journal.pone.0025598
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2011-32_kb_critical_region_excluding-published.pdf1.23 MBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

35
checked on Oct 17, 2019

WEB OF SCIENCETM
Citations

36
checked on Oct 2, 2019

Page view(s)

135
checked on Oct 11, 2019

Download(s)

31
checked on Oct 11, 2019

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.