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GWAS Study

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Hardcastle AJ, Liskova P, Bykhovskaya Y et al.

33649486 PubMed ID
GWAS Study Type
117031 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

HA
Hardcastle AJ
LP
Liskova P
BY
Bykhovskaya Y
MB
McComish BJ
DA
Davidson AE
IC
Inglehearn CF
LX
Li X
CH
Choquet H
HM
Habeeb M
LS
Lucas SEM
SS
Sahebjada S
PN
Pontikos N
LK
Lopez KER
KA
Khawaja AP
AM
Ali M
DL
Dudakova L
SP
Skalicka P
VD
Van Dooren BTH
GA
Geerards AJM
HC
Haudum CW
FV
Faro VL
TA
Tenen A
SM
Simcoe MJ
PK
Patasova K
YD
Yarrand D
YJ
Yin J
SS
Siddiqui S
RA
Rice A
FL
Farraj LA
CY
Chen YI
RJ
Rahi JS
KR
Krauss RM
TE
Theusch E
CJ
Charlesworth JC
SL
Szczotka-Flynn L
TC
Toomes C
MM
Meester-Smoor MA
RA
Richardson AJ
MP
Mitchell PA
TK
Taylor KD
MR
Melles RB
AA
Aldave AJ
MR
Mills RA
CK
Cao K
CE
Chan E
DM
Daniell MD
WJ
Wang JJ
RJ
Rotter JI
HA
Hewitt AW
MS
MacGregor S
KC
Klaver CCW
RW
Ramdas WD
CJ
Craig JE
IS
Iyengar SK
OD
O'Brart D
JE
Jorgenson E
BP
Baird PN
RY
Rabinowitz YS
BK
Burdon KP
HC
Hammond CJ
TS
Tuft SJ
HP
Hysi PG
Chapter II

Abstract

Summary of the research findings

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

2,116 European ancestry cases, 24,626 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

117031
Total Participants
GWAS
Study Type
Yes
Replicated
1, 389 European ancestry cases, 79,727 European ancestry controls, 759 South Asian ancestry cases, 8,009 South Asian ancestry controls, 405 African ancestry cases, 4,185 African ancestry controls
Replication Participants
European, South Asian, African unspecified
Ancestry
U.K., Czech Republic, U.S., Australia
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

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