DOI: 10.5061/dryad.mcvdnck22
title: Long-term development of lens fluorescence in a twin cohort: Heritability and effects of age and lifestyle

description: Background: The blue-green autofluorescence of the ocular lens increases
 with age, glycemia and smoking, as the irreplaceable structural proteins
 of the lens slowly accumulate damage from the encounter with reactive
 molecular species. We have conducted a prospective study of lens
 autofluorescence over two decades in a twin cohort. Methods: The study
 included 131 phakic, non-diabetic adult twins (median age at follow-up 58
 years, range 41-66 years) who were examined twice at an interval of 21
 years. Change in anterior lens peak autofluorescence was analyzed in
 relation to age, current and baseline glycemia, cumulative smoking and
 heritability. Results: The level of lens autofluorescence in the study
 population increased as a function of age and smoking (p ≤.002), but not
 as a function of glycemia (p ≥.069). Lens autofluorescence remained a
 highly heritable trait (90.6 % at baseline and 93.3 % at follow-up), but
 whereas the combined effect of age and cumulative smoking explained 57.2 %
 of the variance in lens autofluorescence at baseline in mid-life, it only
 accounted for 31.6 % at follow-up 21 years later. Conclusion: From mid to
 late adulthood, the level of blue-green fluoescence remained
 overwhelmingly heritable, but became less predictable from age, smoking
 habits and glycemic status. Presumably, as the lens ages, its intrinsic
 characteristics come to dominate over environmental and systemic factors,
 perhaps in a prelude to the development of cataract.
description: <strong>Statistical analysis</strong>
 Statistical analyses were performed in R-Studio v1.2.5001 for
 Windows. Normality was tested by Shapiro-Wilk normality test. Parametric
 data were reported in means with 95 % confidence intervals or standard
 deviations (SD) and compared using Student’s t-test. Non-parametric
 variables were reported in medians and interquartile ranges (IQR) and/or
 full ranges and compared using the Mann-Whitney U test. Lens fluorescence
 was transformed by log10 to obtain normal distributions in all analyses.
 All lens fluorescence values reported have been back-transformed by
 antilog to geometric means with 95 % confidence intervals.
 Univariate and multivariable log-level linear mixed model
 analyses adjusted for twin-pair data clustering were performed with the R
 functions ‘lmer’ (lme4 v.1.1.26 package) and ‘modelTest’ (JWileymisc v.
 1.2.0 package) with adjusted R<sup>2</sup> values reported,
 and coefficient estimates exponentiated and converted to percentages to
 designate the percentage increase in median lens fluorescence per one-unit
 increase in each covariate. Only covariates with statistically significant
 influence on lens fluorescence as found by univariate analysis were
 included in the corresponding multivariable analyses.
 Broad-sense heritability analyses of lens fluorescence were
 performed with the R function ‘twinlm’ (mets v. 1.2.8.1 package) with
 adjustment for covariates that were found to have statistically
 significant effects on lens fluorescence in univariate linear regression
 analyses. Heritability and environmental influences were quantified into
 the coefficients A (additive genetics), D (dominant genetics), C (shared
 environment) and E (non-shared environment) and the broad-sense
 heritability coefficient <i>h<sup>2 
 </sup></i>(A+D), calculated in each of the following
 combinatory heritability models: ACE, ADE, AE, DE and CE. Best-fitting
 heritability models were found by Akaike’s information criterion (AIC),
 with the lowest AIC-value defining the best-fitting model in each analysis
 group. Models with AIC-values between the value of the best fitting model
 and the value of the best fitting model plus two AIC-units were considered
 statistically non-inferior to the best fitting model. P-values below 5 %
 were considered statistically significant in all analyses.
description: Please view the spreadsheet tab "ReadMe_tab" of the
 data file for usage notes.