Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani; Kathryn P. Burdon; Jessica N. Cooke Bailey; Alex W. Hewitt; Matthew H. Law; Louis R. Pasquale; Jae H. Kang; Jonathan L. Haines; Emmanuelle Souzeau; Tiger Zhou; Owen M. Siggs; John Landers; Mona Awadalla; Shiwani Sharma; Richard A. Mills; Bronwyn Ridge; David Lynn; Robert Casson; Stuart L. Graham; Ivan Goldberg; Andrew White; Paul R. Healey; John Grigg; Mitchell Lawlor; Paul Mitchell; Jonathan Ruddle; Michael Coote; Mark Walland; Stephen Best; Andrea Vincent; Jesse Gale; Graham Radfordsmith; David C. Whiteman; Grant W. Montgomery; Nicholas G. Martin; David A. MacKey; Janey L. Wiggs; Stuart MacGregor; Jamie E. Craig; R. Rand Allingham; Murray Brilliant; Donald L. Budenz; John H. Fingert; Douglas Gaasterland; Teresa Gaasterland; Lisa Hark; Michael Hauser; Robert P. Igo; Peter Kraft; Richard K. Lee; Paul R. Lichter; Yutao Liu; Syoko Moroi; Margaret Pericak-Vance; Anthony Realini; Doug Rhee; Julia E. Richards; Robert Ritch; Joel S. Schuman; William K. Scott; Kuldev Singh; Arthur J. Sit; Douglas Vollrath; Gadi Wollstein; Donald J. Zack

doi:10.1038/s41598-018-20435-9

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani, Kathryn P. Burdon, Jessica N. Cooke Bailey, Alex W. Hewitt, Matthew H. Law, Louis R. Pasquale, Jae H. Kang, Jonathan L. Haines, Emmanuelle Souzeau, Tiger Zhou, Owen M. Siggs, John Landers, Mona Awadalla, Shiwani Sharma, Richard A. Mills, Bronwyn Ridge, David Lynn, Robert Casson, Stuart L. Graham, Ivan GoldbergAndrew White, Paul R. Healey, John Grigg, Mitchell Lawlor, Paul Mitchell, Jonathan Ruddle, Michael Coote, Mark Walland, Stephen Best, Andrea Vincent, Jesse Gale, Graham Radfordsmith, David C. Whiteman, Grant W. Montgomery, Nicholas G. Martin, David A. MacKey, Janey L. Wiggs, Stuart MacGregor, Jamie E. Craig, R. Rand Allingham, Murray Brilliant, Donald L. Budenz, John H. Fingert, Douglas Gaasterland, Teresa Gaasterland, Lisa Hark, Michael Hauser, Robert P. Igo, Peter Kraft, Richard K. Lee, Paul R. Lichter, Yutao Liu, Syoko Moroi, Margaret Pericak-Vance, Anthony Realini, Doug Rhee, Julia E. Richards, Robert Ritch, Joel S. Schuman, William K. Scott, Kuldev Singh, Arthur J. Sit, Douglas Vollrath, Gadi Wollstein, Donald J. Zack

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

Abstract

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways-"response to fluid shear stress" and "abnormal retina morphology"-in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

Original language	English (US)
Article number	3124
Journal	Scientific reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-20435-9
State	Published - Dec 1 2018

ASJC Scopus subject areas

General

Access to Document

10.1038/s41598-018-20435-9

Cite this

Gharahkhani, P., Burdon, K. P., Cooke Bailey, J. N., Hewitt, A. W., Law, M. H., Pasquale, L. R., Kang, J. H., Haines, J. L., Souzeau, E., Zhou, T., Siggs, O. M., Landers, J., Awadalla, M., Sharma, S., Mills, R. A., Ridge, B., Lynn, D., Casson, R., Graham, S. L., ... Zack, D. J. (2018). Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma. Scientific reports, 8(1), [3124]. https://doi.org/10.1038/s41598-018-20435-9

Gharahkhani, P, Burdon, KP, Cooke Bailey, JN, Hewitt, AW, Law, MH, Pasquale, LR, Kang, JH, Haines, JL, Souzeau, E, Zhou, T, Siggs, OM, Landers, J, Awadalla, M, Sharma, S, Mills, RA, Ridge, B, Lynn, D, Casson, R, Graham, SL, Goldberg, I, White, A, Healey, PR, Grigg, J, Lawlor, M, Mitchell, P, Ruddle, J, Coote, M, Walland, M, Best, S, Vincent, A, Gale, J, Radfordsmith, G, Whiteman, DC, Montgomery, GW, Martin, NG, MacKey, DA, Wiggs, JL, MacGregor, S, Craig, JE, Allingham, RR, Brilliant, M, Budenz, DL, Fingert, JH, Gaasterland, D, Gaasterland, T, Hark, L, Hauser, M, Igo, RP, Kraft, P, Lee, RK, Lichter, PR, Liu, Y, Moroi, S, Pericak-Vance, M, Realini, A, Rhee, D, Richards, JE, Ritch, R, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Vollrath, D, Wollstein, G & Zack, DJ 2018, 'Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma', Scientific reports, vol. 8, no. 1, 3124. https://doi.org/10.1038/s41598-018-20435-9

@article{8a984d8c439c44158f9a3c36af44c5d7,

title = "Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma",

abstract = "Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways-{"}response to fluid shear stress{"} and {"}abnormal retina morphology{"}-in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.",

author = "Puya Gharahkhani and Burdon, {Kathryn P.} and {Cooke Bailey}, {Jessica N.} and Hewitt, {Alex W.} and Law, {Matthew H.} and Pasquale, {Louis R.} and Kang, {Jae H.} and Haines, {Jonathan L.} and Emmanuelle Souzeau and Tiger Zhou and Siggs, {Owen M.} and John Landers and Mona Awadalla and Shiwani Sharma and Mills, {Richard A.} and Bronwyn Ridge and David Lynn and Robert Casson and Graham, {Stuart L.} and Ivan Goldberg and Andrew White and Healey, {Paul R.} and John Grigg and Mitchell Lawlor and Paul Mitchell and Jonathan Ruddle and Michael Coote and Mark Walland and Stephen Best and Andrea Vincent and Jesse Gale and Graham Radfordsmith and Whiteman, {David C.} and Montgomery, {Grant W.} and Martin, {Nicholas G.} and MacKey, {David A.} and Wiggs, {Janey L.} and Stuart MacGregor and Craig, {Jamie E.} and Allingham, {R. Rand} and Murray Brilliant and Budenz, {Donald L.} and Fingert, {John H.} and Douglas Gaasterland and Teresa Gaasterland and Lisa Hark and Michael Hauser and Igo, {Robert P.} and Peter Kraft and Lee, {Richard K.} and Lichter, {Paul R.} and Yutao Liu and Syoko Moroi and Margaret Pericak-Vance and Anthony Realini and Doug Rhee and Richards, {Julia E.} and Robert Ritch and Schuman, {Joel S.} and Scott, {William K.} and Kuldev Singh and Sit, {Arthur J.} and Douglas Vollrath and Gadi Wollstein and Zack, {Donald J.}",

note = "Funding Information: ANZRAG: Support for recruitment of ANZRAG was provided by the Royal Australian and New Zealand College of Ophthalmology (RANZCO) Eye Foundation. Genotyping was funded by the National Health and Medical Research Council of Australia (#535074 and #1023911). This work was also supported by funding from NHMRC #1031362 awarded to J.E.C., NHMRC #1037838 awarded to A.W.H., NHMRC #1048037 awarded to S.L.G., NHMRC #1009844 awarded to R.J.C. and I.G., NHMRC #1031920 and Alcon Research Institute grant awarded to D.A.M., Allergan Unrestricted grant awarded to A.J.W., and the BrightFocus Foundation and a Ramaciotti Establishment Grant. The authors acknowledge the support of Ms Bronwyn Usher-Ridge in patient recruitment and data collection, and Dr Patrick Danoy and Dr Johanna Hadler for genotyping. Controls for the ANZRAG cohort were drawn from the Australian Cancer Study, the Study of Digestive Health, a study of inflammatory bowel diseases, a study of endometriosis, and QIMR Berghofer twin study. The Australian Cancer Study was supported by the Queensland Cancer Fund and the National Health and Medical Research Council (NHMRC) of Australia (Program no. 199600, awarded to David C. Whiteman, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie, and Penelope M. Webb; and program no. 552429 awarded to David C. Whiteman). The Study of Digestive Health was supported by grant number 5 R01 CA 001833 from the US National Cancer Institute (awarded to David C. Whiteman). The Barrett{\textquoteright}s and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS) sponsored the genotyping of oesophageal cancer and Barrett{\textquoteright}s oesophagus cases, which were used as unscreened controls in the ANZRAG cohort. BEAGESS was funded by grant R01 CA136725 from the US National Cancer Institute. Genotyping for part of the Australian twin control samples included in the ANZRAG cohort was funded by an NHMRC Medical Genomics Grant. Genotyping for the remainder of twin controls was performed by the National Institutes of Health (NIH) Center for Inherited Research (CIDR) as part of an NIH/National Eye Institute (NEI) grant 1RO1EY018246, and we are grateful to Dr Camilla Day and staff. We acknowledge with appreciation all women who participated in the QIMR Berghofer endometriosis study. We thank Endometriosis Associations for supporting study recruitment. We thank Sullivan Nicolaides and Queensland Medical Laboratory for pro bono collection and delivery of blood samples and other pathology services for assistance with blood collection. The QIMR twin and endometriosis studies were supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927,389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1049472 and 1050208), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne), and donations from Neville and Shirley Hawkins. We thank Matthew A. Brown, Margaret J. Wright, Megan J. Campbell, Anthony Caracella, Scott Gordon, Dale R Nyholt, Anjali K Henders, B. Haddon, D. Smyth, H. Beeby, O. Zheng, B. Chapman for their input into project management, databases, sample processing, and genotyping. We are grateful to the many research assistants and interviewers for assistance with the studies contributing to the QIMR Berghofer twin collection. NEIGHBORHOOD: The NEIGHBORHOOD data collection and analysis is supported by NIH/NEI R01EY022305 (JL Wiggs) and NIH/NEI P30 EY014104 (JL Wiggs). Support for collection of cases, controls and analysis for individual datasets is as follows. Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research (CIDR) and were supported by the National Eye Institute through grant HG005259-01 (JL Wiggs). Genotyping for the MEEI dataset and some NHS and HPFS cases (GLAUGEN) was completed at the Broad Institute and supported by GENEVA project grant HG004728 (LR Pasquale) and U01-HG004424 (Broad Institute). Genotype data cleaning and analysis for the GLAUGEN study was supported by U01HG004446 (C Laurie). Collecting and processing samples for the NEIGHBOR dataset was supported by the National Eye Institute through ARRA grants 3R01EY015872-05S1 (JL Wiggs) and 3R01EY019126-02S1 (MA Hauser). Funding for the collection of NEIGHBOR cases and controls was provided by NIH grants: EY015543 (RR Allingham), EY006827 (D Gaasterland); HL73042, HL073389, EY13315 (MA Hauser); CA87969, CA49449, UM1 CA186107, UM1 CA167552, EY009149 (PR Lichter), HG004608 (C McCarty), EY008208 (FA Medeiros), EY015473 (LR Pasquale), EY012118 (M Pericak-Vance), EY015682 (A Realini), EY011671 (JE Richards), EY09580 (JE Richards), EY013178 (JS Schuman), RR015574, EY015872 (JL Wiggs), EY010886 (JL Wiggs), EY009847 (JL Wiggs), EY011008,EY144428 (K Zhang), EY144448 (K Zhang), EY18660 (K Zhang). The collection of Marshfield clinic cases and controls was supported by 1U02HG004608-01, 5U01HG006389-02 and NCATS/NIH grant UL1TR000427. In addition some NHS/HPFS cases and controls and analysis of GWAS data was supported by R01 CA131332. The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. POAG case identification in WGHS was supported by 3R01 EY15473-5S1 (LR Pasquale). JL Wiggs and LR Pasquale are supported by the Harvard Glaucoma Center for Excellence and an unrestricted grant from Research to Prevent Blindness. Dr. Pasquale is also supported by a Harvard Medical School Distinguished Scholar award. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41598-018-20435-9",

language = "English (US)",

volume = "8",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

AU - Gharahkhani, Puya

AU - Burdon, Kathryn P.

AU - Cooke Bailey, Jessica N.

AU - Hewitt, Alex W.

AU - Law, Matthew H.

AU - Pasquale, Louis R.

AU - Kang, Jae H.

AU - Haines, Jonathan L.

AU - Souzeau, Emmanuelle

AU - Zhou, Tiger

AU - Siggs, Owen M.

AU - Landers, John

AU - Awadalla, Mona

AU - Sharma, Shiwani

AU - Mills, Richard A.

AU - Ridge, Bronwyn

AU - Lynn, David

AU - Casson, Robert

AU - Graham, Stuart L.

AU - Goldberg, Ivan

AU - White, Andrew

AU - Healey, Paul R.

AU - Grigg, John

AU - Lawlor, Mitchell

AU - Mitchell, Paul

AU - Ruddle, Jonathan

AU - Coote, Michael

AU - Walland, Mark

AU - Best, Stephen

AU - Vincent, Andrea

AU - Gale, Jesse

AU - Radfordsmith, Graham

AU - Whiteman, David C.

AU - Montgomery, Grant W.

AU - Martin, Nicholas G.

AU - MacKey, David A.

AU - Wiggs, Janey L.

AU - MacGregor, Stuart

AU - Craig, Jamie E.

AU - Allingham, R. Rand

AU - Brilliant, Murray

AU - Budenz, Donald L.

AU - Fingert, John H.

AU - Gaasterland, Douglas

AU - Gaasterland, Teresa

AU - Hark, Lisa

AU - Hauser, Michael

AU - Igo, Robert P.

AU - Kraft, Peter

AU - Lee, Richard K.

AU - Lichter, Paul R.

AU - Liu, Yutao

AU - Moroi, Syoko

AU - Pericak-Vance, Margaret

AU - Realini, Anthony

AU - Rhee, Doug

AU - Richards, Julia E.

AU - Ritch, Robert

AU - Schuman, Joel S.

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur J.

AU - Vollrath, Douglas

AU - Wollstein, Gadi

AU - Zack, Donald J.

N1 - Funding Information: ANZRAG: Support for recruitment of ANZRAG was provided by the Royal Australian and New Zealand College of Ophthalmology (RANZCO) Eye Foundation. Genotyping was funded by the National Health and Medical Research Council of Australia (#535074 and #1023911). This work was also supported by funding from NHMRC #1031362 awarded to J.E.C., NHMRC #1037838 awarded to A.W.H., NHMRC #1048037 awarded to S.L.G., NHMRC #1009844 awarded to R.J.C. and I.G., NHMRC #1031920 and Alcon Research Institute grant awarded to D.A.M., Allergan Unrestricted grant awarded to A.J.W., and the BrightFocus Foundation and a Ramaciotti Establishment Grant. The authors acknowledge the support of Ms Bronwyn Usher-Ridge in patient recruitment and data collection, and Dr Patrick Danoy and Dr Johanna Hadler for genotyping. Controls for the ANZRAG cohort were drawn from the Australian Cancer Study, the Study of Digestive Health, a study of inflammatory bowel diseases, a study of endometriosis, and QIMR Berghofer twin study. The Australian Cancer Study was supported by the Queensland Cancer Fund and the National Health and Medical Research Council (NHMRC) of Australia (Program no. 199600, awarded to David C. Whiteman, Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie, and Penelope M. Webb; and program no. 552429 awarded to David C. Whiteman). The Study of Digestive Health was supported by grant number 5 R01 CA 001833 from the US National Cancer Institute (awarded to David C. Whiteman). The Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study (BEAGESS) sponsored the genotyping of oesophageal cancer and Barrett’s oesophagus cases, which were used as unscreened controls in the ANZRAG cohort. BEAGESS was funded by grant R01 CA136725 from the US National Cancer Institute. Genotyping for part of the Australian twin control samples included in the ANZRAG cohort was funded by an NHMRC Medical Genomics Grant. Genotyping for the remainder of twin controls was performed by the National Institutes of Health (NIH) Center for Inherited Research (CIDR) as part of an NIH/National Eye Institute (NEI) grant 1RO1EY018246, and we are grateful to Dr Camilla Day and staff. We acknowledge with appreciation all women who participated in the QIMR Berghofer endometriosis study. We thank Endometriosis Associations for supporting study recruitment. We thank Sullivan Nicolaides and Queensland Medical Laboratory for pro bono collection and delivery of blood samples and other pathology services for assistance with blood collection. The QIMR twin and endometriosis studies were supported by grants from the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927,389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485, 552498, 1049472 and 1050208), the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne), and donations from Neville and Shirley Hawkins. We thank Matthew A. Brown, Margaret J. Wright, Megan J. Campbell, Anthony Caracella, Scott Gordon, Dale R Nyholt, Anjali K Henders, B. Haddon, D. Smyth, H. Beeby, O. Zheng, B. Chapman for their input into project management, databases, sample processing, and genotyping. We are grateful to the many research assistants and interviewers for assistance with the studies contributing to the QIMR Berghofer twin collection. NEIGHBORHOOD: The NEIGHBORHOOD data collection and analysis is supported by NIH/NEI R01EY022305 (JL Wiggs) and NIH/NEI P30 EY014104 (JL Wiggs). Support for collection of cases, controls and analysis for individual datasets is as follows. Genotyping services for the NEIGHBOR study were provided by the Center for Inherited Disease Research (CIDR) and were supported by the National Eye Institute through grant HG005259-01 (JL Wiggs). Genotyping for the MEEI dataset and some NHS and HPFS cases (GLAUGEN) was completed at the Broad Institute and supported by GENEVA project grant HG004728 (LR Pasquale) and U01-HG004424 (Broad Institute). Genotype data cleaning and analysis for the GLAUGEN study was supported by U01HG004446 (C Laurie). Collecting and processing samples for the NEIGHBOR dataset was supported by the National Eye Institute through ARRA grants 3R01EY015872-05S1 (JL Wiggs) and 3R01EY019126-02S1 (MA Hauser). Funding for the collection of NEIGHBOR cases and controls was provided by NIH grants: EY015543 (RR Allingham), EY006827 (D Gaasterland); HL73042, HL073389, EY13315 (MA Hauser); CA87969, CA49449, UM1 CA186107, UM1 CA167552, EY009149 (PR Lichter), HG004608 (C McCarty), EY008208 (FA Medeiros), EY015473 (LR Pasquale), EY012118 (M Pericak-Vance), EY015682 (A Realini), EY011671 (JE Richards), EY09580 (JE Richards), EY013178 (JS Schuman), RR015574, EY015872 (JL Wiggs), EY010886 (JL Wiggs), EY009847 (JL Wiggs), EY011008,EY144428 (K Zhang), EY144448 (K Zhang), EY18660 (K Zhang). The collection of Marshfield clinic cases and controls was supported by 1U02HG004608-01, 5U01HG006389-02 and NCATS/NIH grant UL1TR000427. In addition some NHS/HPFS cases and controls and analysis of GWAS data was supported by R01 CA131332. The WGHS is supported by HL043851 and HL080467 from the National Heart, Lung, and Blood Institute and CA047988 from the National Cancer Institute, the Donald W. Reynolds Foundation and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. POAG case identification in WGHS was supported by 3R01 EY15473-5S1 (LR Pasquale). JL Wiggs and LR Pasquale are supported by the Harvard Glaucoma Center for Excellence and an unrestricted grant from Research to Prevent Blindness. Dr. Pasquale is also supported by a Harvard Medical School Distinguished Scholar award. Publisher Copyright: © 2018 The Author(s).

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways-"response to fluid shear stress" and "abnormal retina morphology"-in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

AB - Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways-"response to fluid shear stress" and "abnormal retina morphology"-in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

UR - http://www.scopus.com/inward/record.url?scp=85042218563&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042218563&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-20435-9

DO - 10.1038/s41598-018-20435-9

M3 - Article

C2 - 29449654

AN - SCOPUS:85042218563

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 3124

ER -

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this