PMID- 29228253
OWN - NLM
STAT- MEDLINE
DCOM- 20171215
LR  - 20180330
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 14
DP  - 2017 Dec 1
TI  - Rare, Potentially Pathogenic Variants in ZNF469 Are Not Enriched in Keratoconus
      in a Large Australian Cohort of European Descent.
PG  - 6248-6256
LID - 10.1167/iovs.17-22417 [doi]
AB  - Purpose: The Zinc Finger Protein 469 (ZNF469) gene has been proposed as a
      candidate gene for keratoconus due to the association of an upstream polymorphism
      (rs9938149) with the disease in two independent studies, and the role of the gene
      in the autosomal recessive disease Brittle Cornea Syndrome. Coding variants in
      ZNF469 have been assessed for association with keratoconus in several small
      studies, with conflicting results. We assessed rare, potentially pathogenic
      variants in ZNF469 for enrichment in keratoconus patients in a cohort larger than
      all previous studies combined. Methods: ZNF469 was sequenced in 385 Australian
      keratoconus patients of European descent, 346 population controls, and 230
      ethnically matched screened controls by either whole exome sequencing or targeted
      gene sequencing. The frequency of rare and very rare potentially pathogenic
      variants was compared between cases and controls using chi2 or Fisher's exact
      tests and further explored using a gene based test (Sequence Kernel Association
      Test [SKAT]), weighting on the rarity of variants. Results: A total of 49 rare,
      including 33 very rare, potentially pathogenic variants were identified across
      all groups. No enrichment of rare or very rare potentially pathogenic variants in
      ZNF469 was observed in our cases compared to the control groups following
      analysis using chi2 or Fisher's exact tests. This finding was further supported
      by the SKAT results, which found no significant difference in the frequency of
      variants predicted to be damaging between cases and either control group (P =
      0.06). Conclusions: Rare variants in ZNF469 do not contribute to keratoconus
      susceptibility and do not account for the association at rs9938149.
FAU - Lucas, Sionne E M
AU  - Lucas SEM
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania,
      Australia.
FAU - Zhou, Tiger
AU  - Zhou T
AD  - Department of Ophthalmology, Flinders University, Adelaide, South Australia,
      Australia.
FAU - Blackburn, Nicholas B
AU  - Blackburn NB
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania,
      Australia.
AD  - South Texas Diabetes and Obesity Institute, School of Medicine, University of
      Texas Rio Grande Valley, Brownsville, Texas, United States.
FAU - Mills, Richard A
AU  - Mills RA
AD  - Department of Ophthalmology, Flinders University, Adelaide, South Australia,
      Australia.
FAU - Ellis, Jonathan
AU  - Ellis J
AD  - Queensland University of Technology and Translational Research Institute,
      Princess Alexandra Hospital, Brisbane, Queensland, Australia.
FAU - Leo, Paul
AU  - Leo P
AD  - Institute of Health and Biomedical Innovation, Queensland University of
      Technology, Brisbane, Queensland, Australia.
FAU - Souzeau, Emmanuelle
AU  - Souzeau E
AD  - Department of Ophthalmology, Flinders University, Adelaide, South Australia,
      Australia.
FAU - Ridge, Bronwyn
AU  - Ridge B
AD  - Department of Ophthalmology, Flinders University, Adelaide, South Australia,
      Australia.
FAU - Charlesworth, Jac C
AU  - Charlesworth JC
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania,
      Australia.
FAU - Brown, Matthew A
AU  - Brown MA
AD  - Queensland University of Technology and Translational Research Institute,
      Princess Alexandra Hospital, Brisbane, Queensland, Australia.
FAU - Lindsay, Richard
AU  - Lindsay R
AD  - Richard Lindsay and Associates, East Melbourne, Victoria, Australia.
FAU - Craig, Jamie E
AU  - Craig JE
AD  - Department of Ophthalmology, Flinders University, Adelaide, South Australia,
      Australia.
FAU - Burdon, Kathryn P
AU  - Burdon KP
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania,
      Australia.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Transcription Factors)
RN  - 0 (ZNF469 protein, human)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Australia/epidemiology
MH  - DNA/*genetics
MH  - *Ethnic Groups
MH  - Europe/ethnology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Keratoconus/ethnology/*genetics/pathology
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Transcription Factors/*genetics/metabolism
MH  - Zinc Fingers
EDAT- 2017/12/12 06:00
MHDA- 2017/12/16 06:00
CRDT- 2017/12/12 06:00
PHST- 2017/12/12 06:00 [entrez]
PHST- 2017/12/12 06:00 [pubmed]
PHST- 2017/12/16 06:00 [medline]
AID - 2666228 [pii]
AID - 10.1167/iovs.17-22417 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6248-6256. doi:
      10.1167/iovs.17-22417.