Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy

被引：103

作者：

Afshari, Natalie A. ^{[1
]}

Igo, Robert P., Jr. ^{[2
]}

Morris, Nathan J. ^{[2
]}

Stambolian, Dwight ^{[3
]}

Sharma, Shiwani ^{[4
]}

Pulagam, V. Lakshmi ^{[2
]}

Dunn, Steven ^{[5
]}

Stamler, John F. ^{[6
]}

Truitt, Barbara J. ^{[2
]}

Rimmler, Jacqueline ^{[7
]}

Kuot, Abraham ^{[4
]}

Croasdale, Christopher R. ^{[8
]}

Qin, Xuejun ^{[7
]}

Burdon, Kathryn P. ^{[4
,9
]}

Riazuddin, S. Amer ^{[10
]}

Mills, Richard ^{[4
]}

Klebe, Sonja ^{[4
,11
]}

Minear, Mollie A. ^{[7
]}

Zhao, Jiagang ^{[1
]}

Balajonda, Elmer ^{[12
]}

Rosenwasser, George O. ^{[13
]}

Baratz, Keith H. ^{[14
]}

Mootha, V. Vinod ^{[15
]}

Patel, Sanjay V. ^{[14
]}

Gregory, Simon G. ^{[7
]}

Bailey-Wilson, Joan E. ^{[16
,17
]}

Price, Marianne O. ^{[18
]}

Price, Francis W., Jr. ^{[18
]}

Craig, Jamie E. ^{[4
]}

Fingert, John H. ^{[6
]}

Gottsch, John D. ^{[10
]}

Aldave, Anthony J. ^{[19
]}

Klintworth, Gordon K. ^{[12
,20
]}

Lass, Jonathan H. ^{[2
,21
,22
]}

Li, Yi-Ju ^{[7
,23
]}

Iyengar, Sudha K. ^{[2
,21
,22
]}

机构：

[1] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA

[2] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA

[3] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA

[4] Flinders Univ S Australia, Flinders Med Ctr, Dept Ophthalmol, Adelaide, SA 5042, Australia

[5] Michigan Cornea Consultants PC, Southfield, MI 48034 USA

[6] Univ Iowa, Coll Med, Dept Ophthalmol, Iowa City, IA 52242 USA

[7] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC 27701 USA

[8] Davis Duehr Dean Clin, Madison, WI 53715 USA

[9] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7000, Australia

[10] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA

[11] Flinders Univ S Australia, Dept Pathol, Flinders Med Ctr, Adelaide, SA 5042, Australia

[12] Duke Univ, Med Ctr, Duke Univ Eye Ctr, Durham, NC 27710 USA

[13] Cent Penn Eye Inst, Hershey, PA 17033 USA

[14] Mayo Clin, Dept Ophthalmol, Rochester, MN 55905 USA

[15] Univ Texas Southwestern Med Ctr Dallas, Dept Ophthalmol, Dallas, TX 75235 USA

[16] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD 21224 USA

[17] Johns Hopkins Univ, Baltimore, MD 21224 USA

[18] Price Vis Grp, Indianapolis, IN 46260 USA

[19] Univ Calif Los Angeles, Stein Eye Inst, Los Angeles, CA 90095 USA

[20] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA

[21] Case Western Reserve Univ, Dept Ophthalmol & Visual Sci, Cleveland, OH 44106 USA

[22] Univ Hosp Eye Inst, Cleveland, OH 44106 USA

[23] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

澳大利亚国家健康与医学研究理事会; 美国国家卫生研究院;

关键词：

CTG18.1 TRINUCLEOTIDE REPEAT; UNITED-STATES; MISSENSE MUTATIONS; TCF4; GENE; DISEASE; PROTEIN; POLYMORPHISMS; EXPANSION; METAANALYSIS; VARIANTS;

D O I：

10.1038/ncomms14898

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：

The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 x 10(-8)): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.

引用

页数：8

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