TY - JOUR
T1 - Genome-wide association study and meta-analysis of intraocular pressure
AU - Ozel, A. Bilge
AU - Moroi, Sayoko E.
AU - Reed, David M.
AU - Nika, Melisa
AU - Schmidt, Caroline M.
AU - Akbari, Sara
AU - Scott, Kathleen
AU - Rozsa, Frank
AU - Pawar, Hemant
AU - Musch, David C.
AU - Lichter, Paul R.
AU - Gaasterland, Doug
AU - Branham, Kari
AU - Gilbert, Jesse
AU - Garnai, Sarah J.
AU - Chen, Wei
AU - Othman, Mohammad
AU - Heckenlively, John
AU - Swaroop, Anand
AU - Abecasis, Gonçalo
AU - Friedman, David S.
AU - Zack, Don
AU - Ashley-Koch, Allison
AU - Ulmer, Megan
AU - Kang, Jae H.
AU - Liu, Yutao
AU - Yaspan, Brian L.
AU - Haines, Jonathan
AU - Allingham, R. Rand
AU - Hauser, Michael A.
AU - Pasquale, Louis
AU - Wiggs, Janey
AU - Richards, Julia E.
AU - Li, Jun Z.
N1 - Funding Information:
Acknowledgments We acknowledge EY022124 (S.E.M.); 2RO1HL039693 and R01HL112642 (J.Z.L., A.B.O); EY011671, EY09580 (J.E.R.); EY007003 (Michigan Core Center for Vision Research); HG005259-01, 3R01EY015872-05S1, EY015872, EY010886, EY009847 (J.W.); HG004728, EY015473 (L.P.); EY016862, EY007758 (J.R.H.); HG002651 (G.A.); EY009149 (P.R.L.); EY006827 (D.G.); EY016862, EY016862, HL084729, HG002651 (G.R.A.); CA87969, CA49449, CA55075, EY09611 (J.H.K.); T32EY021453 (B.Y.); 3R01EY019126-02S1, EY13315 (M.A.H.); EY015543 (R.R.A.); U01-HG004424 (Broad Institute); HHSN268200782096C; RC1HG005334, U54HG004570 (ENCODE); HG004608 (C.M.M.); HG006389 (C.M.M., M.H.B); EY008208 (F.A.M.); EY015682 (A.R.); EY144428, EY144448, EY18660 (K.Z.); HL073389 (E.H.); U01 HG004446 (C.L.); HG004608 (C.M.); EY008208 (F.A.M.); EY012118, EY012118 (M.A.P–V.); EY015682 (A.R.); EY013178 (J.S.S.); RR015574; EY011008 (L.M.Z.); Other supports included funding from University of Michigan Glaucoma Research Center (S.E.M., J.E.R., J.Z.L.); Ellison Medical Foundation (J.Z.L.); Harvard Glaucoma Center for Excellence, and the Margolis Fund (J.W. and L.P.); Research to Prevent Blindness (A.S., D.C.M., J.W., L.P., J.R.H., and J.E.R.); the Glaucoma Research Foundation (S.E.M., Y.L.); the Glaucoma Foundation (Y.L.); American Health Assistance Foundation (Y.L., J.E.R., J.R.H., A.S.); Elmer and Silvia Sramek Foundation (J.R.H., A.S.); Foundation Fighting Blindness (J.R.H., A.S.); the Macula Vision Research Foundation (J.R.H., A.S.); the Pew Charitable Trusts (J.R.H., A.S.); the Casey Macular Degeneration Center Fund (J.R.H., A.S.); the Marion W. and Edward F. Knight AMD Fund (J.R.H., A.S.); the Harold and Pauline Price Foundation, National Genotyping Centre of Spain (J.R.H., A.S.).
PY - 2014/1
Y1 - 2014/1
N2 - Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10-8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.
AB - Elevated intraocular pressure (IOP) is a major risk factor for glaucoma and is influenced by genetic and environmental factors. Recent genome-wide association studies (GWAS) reported associations with IOP at TMCO1 and GAS7, and with primary open-angle glaucoma (POAG) at CDKN2B-AS1, CAV1/CAV2, and SIX1/SIX6. To identify novel genetic variants and replicate the published findings, we performed GWAS and meta-analysis of IOP in >6,000 subjects of European ancestry collected in three datasets: the NEI Glaucoma Human genetics collaBORation, GLAUcoma Genes and ENvironment study, and a subset of the Age-related Macular Degeneration-Michigan, Mayo, AREDS and Pennsylvania study. While no signal achieved genome-wide significance in individual datasets, a meta-analysis identified significant associations with IOP at TMCO1 (rs7518099-G, p = 8.0 × 10-8). Focused analyses of five loci previously reported for IOP and/or POAG, i.e., TMCO1, CDKN2B-AS1, GAS7, CAV1/CAV2, and SIX1/SIX6, revealed associations with IOP that were largely consistent across our three datasets, and replicated the previously reported associations in both effect size and direction. These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk.
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U2 - 10.1007/s00439-013-1349-5
DO - 10.1007/s00439-013-1349-5
M3 - Article
C2 - 24002674
AN - SCOPUS:84891865046
SN - 0340-6717
VL - 133
SP - 41
EP - 57
JO - Human Genetics
JF - Human Genetics
IS - 1
ER -