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Roberta Farci, Maria Pina Concas, Ginevra Biino, Vaccargiu Simona, Cristina Malloci, Gianfranca Cappai, Pietro Emanuele Napoli, Mario Pirastu, Maurizio Fossarello; Epidemiology and genetics of TBUT in a Sardinian genetic isolate. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2509.
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<br /> Evaluation of tear break-up time (TBUT) is a simple tool to assess the stability of the preocular tear film. To date, most research on tear film stability focused on environmental risk factors, and little is known about the role of genetics. Our aim is to find some of the factors influencing tear film stability in a Sardinian isolate taking advantage of the high environmental and genetic homogeneity of its population of which we have complete genealogical records.
<br /> A multidisciplinary epidemiologic survey was conducted in two secluded villages of the central eastern Sardinia (Ogliastra). Participants (n=2593) underwent a complete eye examination including TBUT test. Subjects were genotyped using Illumina Human Exome BeadChip array. Correlation of TBUT with more than 100 traits was investigated using linear regression models. GWAS and linkage analysis were performed on both TBUT as a quantitative trait (n=2262, mean value of both eyes) and as a binary trait: cases (TBUT≤5s in both eye, n=133) and controls (TBUT≥10s, n=1468). After quality controls about 48k SNVs (MAF >0.01) were used for GWAS assessing genotype-phenotype association by linear regression analysis under an additive effect model, adjusting for age, gender and relatedness as implemented in GenABEL. Variance component and nonparametric linkage analyses were performed using MERLIN and a subset of SNVs (~20K after clustering for linkage disequilibrium).
<br /> Standardized prevalence of TBUT ≤5s was 8% (95% CI: 7.1%-9.0%), with no significant gender differences. On average, TBUT decreases of about 0.8s for each 10 years increase in age, it is 0.8s lower in women, it decreases with increasing BMI and cell mean corpuscular volume, but it rises 0.12s for each 1D increase in spherical equivalents (P<0.05). TBUT heritability was about 10%. GWAS of quantitative TBUT (Bonferroni significant threshold 1.1x10-6) revealed several suggestive loci: i.e. PRL (P=5.4x10-5), FBLN2 (P=6.7 x10-6), AKAP13 (P=8.98 x10-5). In GWAS of binary trait, we found a suggestive signal in DNAH10 gene (P=1.67x10-5). Linkage analysis showed a signal for quantitative TBUT on chr 1p32.2 (LOD=2.39) and one for the binary trait on chr 11q22.3 (LOD=2).
<br /> This is the first population based study on genetics of TBUT. Using different approaches we identified several suggestive genes/loci some of which already been described associated with eye physiology and pathologies.
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