Yazar Seyhan, Cuellar-Partida Gabriel, McKnight Charlotte M, Quach-Thanissorn Piriya, Mountain Jenny A, Coroneo Minas T, Pennell Craig E, Hewitt Alex W, MacGregor Stuart, Mackey David A
Centre for Ophthalmology and Vision Science/Lions Eye Institute Perth, University of Western Australia, Perth, Australia.
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
JAMA Ophthalmol. 2015 Apr;133(4):406-12. doi: 10.1001/jamaophthalmol.2014.5627.
Conjunctival UV autofluorescence (CUVAF) photography was developed to detect and characterize preclinical sunlight-induced ocular damage. Ocular sun exposure has been related to cases of pterygia and was recently negatively correlated with myopia. Hence, CUVAF has excellent potential as an objective biomarker of sun exposure. However, much variation in CUVAF has been observed, and the relative contributions of genes and environment to this variation have not yet been identified.
To investigate sources of variation in CUVAF in relation to its potential clinical relevance.
DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional analysis of 3 population-based cohort studies in the general community, including the Twins Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and 2009, and the 20-year follow-up of the Raine Study was completed between March 2010 and February 2012. We included genotypic and phenotypic data from 295 Australian families in the Tasmanian and Brisbane twin studies and from 661 participants in the 20-year follow-up of the Raine Study. We compared CUVAF levels in the 3 cohorts and performed a classic twin study to partition variation in CUVAF. We also conducted a genome-wide association analysis to identify specific genetic variants associated with CUVAF.
The total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms (SNPs) associated with CUVAF from the genome-wide association study.
Within twin cohorts, individuals living closer to the equator (latitude, 27.47° S) had higher levels of CUVAF compared with individuals from southern regions (latitude, 42.88° S) (median [interquartile range], 45.4 [26.8-68.5] vs 28.7 [15.0-42.3] mm2; P < .001). The variation in CUVAF explained by the additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043, located approximately 800 base pairs away from the SLC1A5 gene, a member of the solute carrier family 1, had a genome-wide significant association with a P value of 3.2 × 10-8. Gene-based analysis did not improve our power to detect association with other genes.
Our findings confirm that, although a large environmental component to CUVAF (equivalent of sun exposure) exists, genes also play a significant role. We identified a SNP (rs1060043) as being significantly associated with CUVAF; replication of this finding in future studies is warranted.
结膜紫外线自发荧光（CUVAF）摄影技术被用于检测和表征临床前阳光诱导的眼部损伤。眼部阳光暴露与翼状胬肉病例相关，且最近与近视呈负相关。因此，CUVAF作为阳光暴露的客观生物标志物具有巨大潜力。然而，已观察到CUVAF存在很大差异，基因和环境对这种差异的相对贡献尚未明确。
研究CUVAF变异的来源及其潜在的临床相关性。
设计、背景和参与者：我们对普通社区中3项基于人群的队列研究进行了横断面分析，包括塔斯马尼亚双胞胎眼研究、布里斯班青少年双胞胎研究和西澳大利亚妊娠队列（Raine）研究。双胞胎研究于2001年至2009年进行，Raine研究的20年随访于2010年3月至2012年2月完成。我们纳入了塔斯马尼亚和布里斯班双胞胎研究中295个澳大利亚家庭的基因型和表型数据，以及Raine研究20年随访中的661名参与者的数据。我们比较了3个队列中的CUVAF水平，并进行了经典双胞胎研究以划分CUVAF的变异。我们还进行了全基因组关联分析以识别与CUVAF相关的特定基因变异。
CUVAF的总面积、CUVAF的遗传力以及全基因组关联研究中与CUVAF相关的单核苷酸多态性（SNP）。
在双胞胎队列中，生活在更靠近赤道（南纬27.47°）的个体与来自南部地区（南纬42.88°）的个体相比，CUVAF水平更高（中位数[四分位间距]，45.4[26.8 - 68.5] vs 28.7[15.0 - 42.3]mm²；P <.001）。由加性遗传成分解释的CUVAF变异为0.37（95%CI，0.22 - 0.56），而由共同环境导致的变异为0.50（95%CI；0.29 - 0.71）。位于溶质载体家族1成员SLC1A5基因约800个碱基对处的SNP rs1060043与全基因组具有显著关联，P值为3.2×10⁻⁸。基于基因的分析并未提高我们检测与其他基因关联的能力。
我们的研究结果证实，尽管CUVAF存在很大的环境因素（相当于阳光暴露），但基因也起着重要作用。我们确定了一个与CUVAF显著相关的SNP（rs1060043）；未来研究有必要对这一发现进行重复验证。
