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A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort

A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort
A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort
Glaucoma is a major cause of blindness in the world. To date, common genetic variants associated with glaucoma only explain a small proportion of its heritability. We performed a genome-wide association study of intra-ocular pressure (IOP), an underlying endophenotype for glaucoma. The discovery phase of the study was carried out in the TwinsUK cohort (N = 2774) analyzing association between IOP and single nucleotide polymorphisms (SNPs) imputed to HapMap2. The results were validated in 12 independent replication cohorts of European ancestry (combined N = 22 789) that were a part of the International Glaucoma Genetics Consortium. Expression quantitative trait locus (eQTL) analyses of the significantly associated SNPs were performed using data from the Multiple Tissue Human Expression Resource (MuTHER) Study. In the TwinsUK cohort, IOP was significantly associated with a number of SNPs at 9q33.3 (P = 3.48 × 10(-8) for rs2286885, the most significantly associated SNP at this locus), within the genomic sequence of the FAM125B gene. Independent replication in a composite panel of 12 cohorts revealed consistent direction of effect and significant association (P = 0.003, for fixed-effect meta-analysis). Suggestive evidence for an eQTL effect of rs2286885 was observed for one of the probes targeting the coding region of the FAM125B gene. This gene codes for a component of a membrane complex involved in vesicular trafficking process, a function similar to that of the Caveolin genes (CAV1 and CAV2) which have previously been associated with primary open-angle glaucoma. This study suggests a novel association between SNPs in FAM125B and IOP in the TwinsUK cohort, though further studies to elucidate the functional role of this gene in glaucoma are necessary.
3343-3348
Nag, A.
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Small, K.S.
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Uitterlinden, A.G.
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van Duijn, C.M.
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van Koolwijk, L.M.
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Vingerling, J.R.
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Xu, L.
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Yonova-Doing, E.
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Tanja, Z.
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Nag, A.
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Mackey, D.A.
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Hysi, P.G.
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Hammond, C.
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Aung, T.
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Gibson, J.
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Hewitt, A.W.
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Mitchell, P.
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Ramdas, W.D.
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Uitterlinden, A.G.
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Wong, T.-Y.
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WTCCC, None
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Xu, L.
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Yonova-Doing, E.
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Tanja, Z.
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Nag, A., Venturini, C., Small, K.S., Young, T. L., Viswanathan, A.C., Mackey, D.A., Hysi, P.G., Hammond, C., Aung, T., Cheng, C.-Y., Fleck, B.W., Gibson, J., Hewitt, A.W., Hofman, A., Hohn, R., Jonas, J.B., Khor, C.-C., Klaver, C.C., Lemij, H.G., Liao, J., Lotery, A.J., Lu, Y., Macgregor, S., Mitchell, P., Ramdas, W.D., Springelkamp, H., Tai, E.-S., Teo, Y.-Y., Uitterlinden, A.G., van Duijn, C.M., van Koolwijk, L.M., Vingerling, J.R., Vitart, V., Vithana, E., Wang, J.J., Williams, K.M., Wojciechowski, R., Wong, T.-Y., WTCCC, None, Xu, L., Yonova-Doing, E. and Tanja, Z. (2014) A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort. Human Molecular Genetics, 23 (12), 3343-3348. (doi:10.1093/hmg/ddu050). (PMID:24518671)

Record type: Article

Abstract

Glaucoma is a major cause of blindness in the world. To date, common genetic variants associated with glaucoma only explain a small proportion of its heritability. We performed a genome-wide association study of intra-ocular pressure (IOP), an underlying endophenotype for glaucoma. The discovery phase of the study was carried out in the TwinsUK cohort (N = 2774) analyzing association between IOP and single nucleotide polymorphisms (SNPs) imputed to HapMap2. The results were validated in 12 independent replication cohorts of European ancestry (combined N = 22 789) that were a part of the International Glaucoma Genetics Consortium. Expression quantitative trait locus (eQTL) analyses of the significantly associated SNPs were performed using data from the Multiple Tissue Human Expression Resource (MuTHER) Study. In the TwinsUK cohort, IOP was significantly associated with a number of SNPs at 9q33.3 (P = 3.48 × 10(-8) for rs2286885, the most significantly associated SNP at this locus), within the genomic sequence of the FAM125B gene. Independent replication in a composite panel of 12 cohorts revealed consistent direction of effect and significant association (P = 0.003, for fixed-effect meta-analysis). Suggestive evidence for an eQTL effect of rs2286885 was observed for one of the probes targeting the coding region of the FAM125B gene. This gene codes for a component of a membrane complex involved in vesicular trafficking process, a function similar to that of the Caveolin genes (CAV1 and CAV2) which have previously been associated with primary open-angle glaucoma. This study suggests a novel association between SNPs in FAM125B and IOP in the TwinsUK cohort, though further studies to elucidate the functional role of this gene in glaucoma are necessary.

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e-pub ahead of print date: 11 February 2014
Published date: 15 June 2014
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 368924
URI: http://eprints.soton.ac.uk/id/eprint/368924
DOI: doi:10.1093/hmg/ddu050
PURE UUID: 26be191c-c930-44f5-8a57-3afb4ceec5f4
ORCID for J. Gibson: ORCID iD orcid.org/0000-0002-0973-8285
ORCID for A.J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 15 Sep 2014 08:54
Last modified: 15 Mar 2024 03:17

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Contributors

Author: A. Nag
Author: C. Venturini
Author: K.S. Small
Author: T. L. Young
Author: A.C. Viswanathan
Author: D.A. Mackey
Author: P.G. Hysi
Author: C. Hammond
Author: T. Aung
Author: C.-Y. Cheng
Author: B.W. Fleck
Author: J. Gibson ORCID iD
Author: A.W. Hewitt
Author: A. Hofman
Author: R. Hohn
Author: J.B. Jonas
Author: C.-C. Khor
Author: C.C. Klaver
Author: H.G. Lemij
Author: J. Liao
Author: A.J. Lotery ORCID iD
Author: Y. Lu
Author: S. Macgregor
Author: P. Mitchell
Author: W.D. Ramdas
Author: H. Springelkamp
Author: E.-S. Tai
Author: Y.-Y. Teo
Author: A.G. Uitterlinden
Author: C.M. van Duijn
Author: L.M. van Koolwijk
Author: J.R. Vingerling
Author: V. Vitart
Author: E. Vithana
Author: J.J. Wang
Author: K.M. Williams
Author: R. Wojciechowski
Author: T.-Y. Wong
Author: None WTCCC
Author: L. Xu
Author: E. Yonova-Doing
Author: Z. Tanja

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