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Originally published In Press as doi:10.1167/iovs.09-3577 on May 6, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:5115-5119.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.09-3577
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Repeated Measures of Intraocular Pressure Result in Higher Heritability and Greater Power in Genetic Linkage Studies

Francis Carbonaro,1 Toby Andrew,1 David A. Mackey,2 Terri L. Young,3 Tim D. Spector,1 and Christopher J. Hammond1,4

From the 1Department of Twin Research and Genetic Epidemiology, King's College London School of Medicine, London, United Kingdom; the 2Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia; the 3Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; and the 4Princess Royal University Hospital, Bromley Hospitals NHS Trust, Orpington, United Kingdom.

Corresponding author: Francis Carbonaro, Department of Twin Research and Genetic Epidemiology, St. Thomas' Hospital, London, UK; francis.carbonaro{at}btopenworld.com.

Purpose. To analyze the effect of using one reading, the mean of two readings (from the same eye), or the mean of four readings (two from each eye) on the heritability estimates of intraocular pressure (IOP). This was a cohort study in which 344 pairs of twins, 163 monozygotic (MZ) and 181 dizygotic (DZ), were enrolled.

Methods. IOP was measured using three tonometers: the gold standard Goldmann applanation tonometer (GAT), the Ocular Response Analyzer (ORA; Reichert Buffalo, NY), and the Dynamic Contour Tonometer (DCT, Pascal; Swiss Microtechnology AG, Port, Switzerland). The main outcome measure was the heritability of IOP correlated with the number of measurements.

Results. The mean IOPs of all four readings with the three tonometers were: 14.1 ± 2.9 mm Hg for GAT, 15.9 ± 3.2 mm Hg for ORA, and 16.9 ± 2.7 mm Hg for DCT. As the number of readings increased, the calculated heritability (h2) of IOP measured using the GAT readings increased from 0.56 for one reading (95% confidence interval [CI], 0.44–0.65) to 0.58 for the mean of two readings (95% CI, 0.46–0.67) to 0.64 for the mean of all four readings (two right and two left; 95% CI, 0.55–0.72). Similar results were seen with the other two instruments.

Conclusions. The results demonstrated that the use of the mean of several readings from both eyes reduced measurement error, yielding a higher heritability estimate. The higher heritability would increase the power to detect linkage in a genome-wide analysis.






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