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

Gharahkhani, Puya, Burdon, Kathryn P., Cooke Bailey, Jessica N, Hewitt, Alex W., Law, Matthew H., Pasquale, Louis R., Kang, Jae H., Haines, Jonathan L., Souzeau, Emmanuelle, Zhou, Tiger, Siggs, Owen M., Landers, John, Awadalla, Mona, Sharma, Shiwani, Mills, Richard A., Ridge, Bronwyn, Lynn, David, Casson, Robert, Graham, Stuart L., Goldberg, Ivan, White, Andrew, Healey, Paul R., Grigg, John, Lawlor, Mitchell, Mitchell, Paul, Ruddle, Jonathan, Coote, Michael, Walland, Mark, Best, Stephen, Vincent, Andrea, Gale, Jesse, RadfordSmith, Graham, Whiteman, David C., Montgomery, Grant W., Martin, Nicholas G., Mackey, David A., Wiggs, Janey L., MacGregor, Stuart, Craig, Jamie E. and NEIGHBORHOOD consortium (2018) Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma. Scientific reports, 8 1: 3124. doi:10.1038/s41598-018-20435-9

Author Gharahkhani, Puya
Burdon, Kathryn P.
Cooke Bailey, Jessica N
Hewitt, Alex W.
Law, Matthew H.
Pasquale, Louis R.
Kang, Jae H.
Haines, Jonathan L.
Souzeau, Emmanuelle
Zhou, Tiger
Siggs, Owen M.
Landers, John
Awadalla, Mona
Sharma, Shiwani
Mills, Richard A.
Ridge, Bronwyn
Lynn, David
Casson, Robert
Graham, Stuart L.
Goldberg, Ivan
White, Andrew
Healey, Paul R.
Grigg, John
Lawlor, Mitchell
Mitchell, Paul
Ruddle, Jonathan
Coote, Michael
Walland, Mark
Best, Stephen
Vincent, Andrea
Gale, Jesse
RadfordSmith, Graham
Whiteman, David C.
Montgomery, Grant W.
Martin, Nicholas G.
Mackey, David A.
Wiggs, Janey L.
MacGregor, Stuart
Craig, Jamie E.
Title Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma
Journal name Scientific reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2018-02-15
Year available 2018
Sub-type Article (original research)
DOI 10.1038/s41598-018-20435-9
Open Access Status DOI
Volume 8
Issue 1
Start page 3124
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
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.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R01 EY011671
U01 HG004728
U01 HG004446
R21 EY028671
R01 EY018246
UL1 TR000427
R01 EY011008
P01 CA087969
R01 HL043851
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P01 HL073042
U01 HG004424
R01 HL073389
R01 EY012118
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R56 EY011671
U01 HG006389
R01 EY008208
R01 CA136725
R01 EY013178
R01 EY019126
R03 EY015682
R01 EY022305
P20 RR015574
UM1 CA186107
R01 EY015473
R01 CA047988
R01 HL080467
UM1 CA167552
R01 EY009580
U10 EY012118
R01 CA049449
R01 CA131332
P30 EY014104
R01 EY015872
R01 EY009847
R01 EY010886
U01 CA049449
U01 HG004608
R01 EY013315
R01 EY018660
Institutional Status UQ

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Created: Wed, 21 Feb 2018, 11:03:44 EST