TY - JOUR
T1 - Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy
AU - Afshari, Natalie
AU - Igo, Robert
AU - Morris, Nathan
AU - Stambolian, Dwight
AU - Sharma, Shiwani
AU - V, Lakshmi
AU - Dunn, Steven
AU - Stamler, John
AU - Truitt, Barbara
AU - Rimmler, Jacqueline
AU - Kuot, Abraham
AU - Qin, Xuejun
AU - Croasdale, Christopher
AU - Burdon, Kathryn
AU - Riazuddin, S
AU - Mills, Richard
AU - Klebe, Sonja
AU - Minear, Mollie
AU - Zhao, Jiagang
AU - Balajonda, Elmer
AU - Rosenwasser, George
AU - Baratz, Keith
AU - Mootha, V
AU - Patel, Sanjay
AU - Gregory, Simon
AU - Bailey-Wilson, Joan
AU - Price, Marianne
AU - Price, Francis
AU - Craig, Jamie
AU - Fingert, John
AU - Gottsch, John
AU - Aldave, Anthony
AU - Klintworth, Gordon
AU - Lass, Jonathan
AU - Li, Yi
AU - Iyengar, Sudha
PY - 2017/3/30
Y1 - 2017/3/30
N2 - 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 × 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.
AB - 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 × 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.
UR - http://www.scopus.com/inward/record.url?scp=85016619002&partnerID=8YFLogxK
U2 - 10.1038/ncomms14898
DO - 10.1038/ncomms14898
M3 - Article
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
M1 - 14898
ER -