Genome-wide association studies have identified the CDC7-TGFBR3 intergenic region on chromosome 1 to be strongly associated with optic disc area size. The mechanism of its function remained unclear until new data on eQTL markers emerged from the Genotype-Tissue Expression project. The target region was found to contain a strong silencer of the distal (800 kb) Transcription Factor (TF) gene GFI1 (Growth Factor Independent Transcription Repressor 1) specifically in neuroendocrine cells (pituitary gland). GFI1 has also been reported to be involved in the development of sensory neurons and hematopoiesis. Therefore, GFI1, being a developmental gene, is likely to affect optic disc area size by altering the expression of the associated genes via long-range interactions. Distribution of haplotypes in the putative enhancer region has been assessed using the data on four continental supergroups generated by the 1000 Genomes Project. The East Asian (EAS) populations were shown to manifest a highly homogenous unimodal haplotype distribution pattern within the region with the major haplotype occurring with the frequency of 0.9. Another European specific haplotype was observed with the frequency of 0.21. The major haplotype appears to be involved in silencing GFI1repressor gene expression, which might be the cause of increased optic disc area characteristic of the EAS populations. The enhancer/eQTL region overlaps AluJo element, which implies that this particular regulatory element is primate-specific and confined to few tissues. Population specific distribution of GFI1 enhancer alleles may predispose certain ethnic groups to glaucoma.

中文翻译：

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分析视盘形态的推定增强子

全基因组关联研究已确定染色体1上的CDC7-TGFBR3基因间区域与视盘面积大小密切相关。直到从基因型组织表达项目中获得有关eQTL标记的新数据之前，其功能机制仍不清楚。发现目标区域在神经内分泌细胞（垂体）中含有一个远端（800 kb）转录因子（TF）基因GFI1（非生长因子转录抑制因子1）的强沉默子。据报道，GFI1也参与感觉神经元和造血作用的发展。因此，GFI1是一种发育基因，它可能通过远距离相互作用改变相关基因的表达，从而影响视盘面积。利用1000基因组计划产生的四个大陆超群的数据，对推定的增强子区域的单倍型分布进行了评估。显示东亚（EAS）人口在该区域内表现出高度同质的单峰单倍型分布模式，主要单倍型的发生频率为0.9。观察到另一欧洲特定单倍型，频率为0.21。主要的单体型似乎与沉默GFI1repressor基因表达有关，这可能是EAS人群视盘面积增加的原因。增强子/ eQTL区域与AluJo元件重叠，这意味着该特定的调控元件是灵长类特异性的，并局限于少数组织。