TY - JOUR
T1 - Evaluation of the Myocilin Mutation Gln368Stop Demonstrates Reduced Penetrance for Glaucoma in European Populations
AU - Nag, Abhishek
AU - Lu, Han
AU - Arno, Matthew
AU - Iglesias, Adriana I.
AU - Bonnemaijer, Pieter
AU - Broer, Linda
AU - Uitterlinden, Andre G.
AU - Klaver, Caroline C.W.
AU - van Duijn, Cornelia
AU - Hysi, Pirro G.
AU - Hammond, Christopher J.
N1 - Publisher Copyright:
© 2016 American Academy of Ophthalmology
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Purpose Sequence variations in the myocilin (MYOC) gene account for approximately 2% to 4% of glaucoma cases. One particular MYOC mutation, Gln368Stop (dbSNP accession number: rs74315329), is the most common genetic mutation causing glaucoma by increasing intraocular pressure (IOP). The objective of this study was to evaluate the effect of this MYOC mutation on IOP using data from large-scale European population panels (directly sequenced and imputation based). Design Cross-sectional, cohort study. Participants For this study, the penetrance of the variant rs74315329 was estimated in 2 population-based cohorts, the TwinsUK (N = 6092) and the Rotterdam Study (RS) (N =11 189). Methods Carriers of the risk allele for rs74315329 were identified using whole-genome sequencing and imputation data (based on 1000 Genomes Project and Haplotype Reference Consortium panels). The penetrance of this variant was evaluated using IOP measurements and data on visual field testing/a diagnosis of glaucoma (if available). Main Outcome Measures The penetrance of the variant rs74315329 was estimated from the percentage of the carriers of the risk allele of the variant who had high IOP (ocular hypertension) or glaucoma. Results In our study, the observed penetrance of the variant rs74315329 in relation to increased IOP was 12.5% and 19.4% in the TwinsUK and the RS, respectively. Thus, our study suggests a much lower penetrance for rs74315329 for ocular hypertension (and thus glaucoma), in comparison with that reported previously. Conclusions The significance of this finding is that higher numbers of healthy individuals in the population are expected to be carriers of this mutation, which in turn reduces the utility of identifying carriers of this mutation as a screening tool for glaucoma.
AB - Purpose Sequence variations in the myocilin (MYOC) gene account for approximately 2% to 4% of glaucoma cases. One particular MYOC mutation, Gln368Stop (dbSNP accession number: rs74315329), is the most common genetic mutation causing glaucoma by increasing intraocular pressure (IOP). The objective of this study was to evaluate the effect of this MYOC mutation on IOP using data from large-scale European population panels (directly sequenced and imputation based). Design Cross-sectional, cohort study. Participants For this study, the penetrance of the variant rs74315329 was estimated in 2 population-based cohorts, the TwinsUK (N = 6092) and the Rotterdam Study (RS) (N =11 189). Methods Carriers of the risk allele for rs74315329 were identified using whole-genome sequencing and imputation data (based on 1000 Genomes Project and Haplotype Reference Consortium panels). The penetrance of this variant was evaluated using IOP measurements and data on visual field testing/a diagnosis of glaucoma (if available). Main Outcome Measures The penetrance of the variant rs74315329 was estimated from the percentage of the carriers of the risk allele of the variant who had high IOP (ocular hypertension) or glaucoma. Results In our study, the observed penetrance of the variant rs74315329 in relation to increased IOP was 12.5% and 19.4% in the TwinsUK and the RS, respectively. Thus, our study suggests a much lower penetrance for rs74315329 for ocular hypertension (and thus glaucoma), in comparison with that reported previously. Conclusions The significance of this finding is that higher numbers of healthy individuals in the population are expected to be carriers of this mutation, which in turn reduces the utility of identifying carriers of this mutation as a screening tool for glaucoma.
UR - http://www.scopus.com/inward/record.url?scp=85009253046&partnerID=8YFLogxK
U2 - 10.1016/j.ophtha.2016.11.018
DO - 10.1016/j.ophtha.2016.11.018
M3 - Article
C2 - 28038983
AN - SCOPUS:85009253046
SN - 0161-6420
VL - 124
SP - 547
EP - 553
JO - Ophthalmology
JF - Ophthalmology
IS - 4
ER -