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

被引：30

作者：

Gharahkhani, Puya ^{[1
]}

Burdon, Kathryn P. ^{[2
]}

Bailey, Jessica N. Cooke ^{[3
]}

Hewitt, Alex W. ^{[2
]}

Law, Matthew H. ^{[1
]}

Pasquale, Louis R. ^{[4
,5
]}

Kang, Jae H. ^{[5
]}

Haines, Jonathan L. ^{[3
]}

Souzeau, Emmanuelle ^{[6
]}

Zhou, Tiger ^{[6
]}

Siggs, Owen M. ^{[6
]}

Landers, John ^{[6
]}

Awadalla, Mona ^{[6
]}

Sharma, Shiwani ^{[6
]}

Mills, Richard A. ^{[6
]}

Ridge, Bronwyn ^{[6
]}

Lynn, David ^{[7
]}

Casson, Robert ^{[8
]}

Graham, Stuart L. ^{[9
]}

Goldberg, Ivan ^{[10
]}

White, Andrew ^{[10
,11
]}

Healey, Paul R. ^{[10
,11
]}

Grigg, John ^{[10
]}

Lawlor, Mitchell ^{[10
]}

Mitchell, Paul ^{[11
]}

Ruddle, Jonathan ^{[12
]}

Coote, Michael ^{[12
]}

Walland, Mark ^{[12
]}

Best, Stephen ^{[13
]}

Vincent, Andrea ^{[13
]}

Gale, Jesse ^{[14
]}

RadfordSmith, Graham ^{[1
,15
]}

Whiteman, David C. ^{[1
]}

Montgomery, Grant W. ^{[1
,16
]}

Martin, Nicholas G. ^{[1
]}

Mackey, David A. ^{[2
,17
]}

Wiggs, Janey L. ^{[4
]}

MacGregor, Stuart ^{[1
]}

Craig, Jamie E. ^{[6
]}

机构：

[1] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[2] Univ Tasmania, Hobart, Tas, Australia

[3] Case Western Reserve Univ, Sch Med, Inst Computat Biol, Populat & Quantitat Hlth Sci, Cleveland, OH USA

[4] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA

[5] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA

[6] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA, Australia

[7] Flinders Univ S Australia, Sch Med, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia

[8] Univ Adelaide, South Australian Inst Ophthalmol, Adelaide, SA, Australia

[9] Macquarie Univ, Ophthalmol & Vis Sci, Sydney, NSW, Australia

[10] Univ Sydney, Dept Ophthalmol, Sydney, NSW, Australia

[11] Univ Sydney, Westmead Inst Med Res, Ctr Vis Res, Westmead, NSW, Australia

[12] Univ Melbourne, Royal Victorian Eye & Ear Hosp, CERA, Melbourne, Vic, Australia

[13] Univ Auckland, Dept Ophthalmol, Auckland, New Zealand

[14] Univ Otago, Dept Ophthalmol, Dunedin, Otago, New Zealand

[15] Univ Queensland, Sch Med, Herston Campus, Brisbane, Qld, Australia

[16] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[17] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

英国医学研究理事会; 美国国家卫生研究院; 澳大利亚国家健康与医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; TO-DISC RATIO; SUSCEPTIBILITY LOCI; TRABECULAR MESHWORK; GENOTYPE IMPUTATION; COMMON VARIANTS; RETINOIC ACID; PROTEIN; DEGENERATION; MULTIPLE;

D O I：

10.1038/s41598-018-20435-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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