Abstract
Ionising radiation (IR) is an environmental factor known to alter genomes and therefore challenge organisms to adapt. Lithuanian clean-up workers of the Chernobyl nuclear disaster (LCWC) experienced high doses of IR, leading to different consequences. This study aims to characterise a unique protective genomic variation in a relatively healthy LCWC group. This variation influenced their individual reaction to IR and potentially protects against certain diseases such as exfoliation syndrome and glaucoma. Clinical and IR dosage data were collected using a questionnaire to characterise the cohort of 93 LCWC. Genome-wide genotyping using Illumina beadchip technology was performed. The control group included 466 unrelated, self-reported healthy individuals of Lithuanian descent. Genotypes were filtered out from the microarray dataset using a catalogue of SNPs. The data were used to perform association, linkage disequilibrium, and epistasis analysis. Phenotype data analysis showed the distribution of the most common disease groups among the LCWC. A genomic variant of statistical significance (Fishers’ exact test, p = 0.019), rs3825942, was identified in LOXL1 (NM_005576.4:c.458G>A). Linkage disequilibrium and epistasis analysis for this variant identified the genes LHFPL3, GALNT6, PIH1D1, ANKS1B, and METRNL as potentially involved in the etiopathogenesis of exfoliation syndrome and glaucoma, which were not previously associated with the disease. The LOXL1 variant is mostly considered a risk factor in the development of exfoliation syndrome and glaucoma. The influence of recent positive selection, the phenomenon of allele-flipping, and the fact that only individuals with the homozygous reference allele have glaucoma in the cohort of the LCWC suggest otherwise. The identification of rs3825942 and other potentially protective genomic variants may be useful for further analysis of the genetic architecture and etiopathogenetic mechanisms of other multifactorial diseases.
Highlights
We found one association with the LOXL1 gene variant which is known for its role in exfoliation syndrome (XFS) manifestation and glaucoma
The incidence of XFS and glaucoma is associated with LOXL1 risk and/or protective genomic variants
We identified a genomic variant in LOXL1
Summary
Natural selection is one of the main evolutionary forces causing species to adapt to their changing environment, as the most advantageous survival traits are selected. The distribution of common genetic variants and fixation of pathogenic ones under the effect of natural selection is crucial for the survival and longevity of a population [1]. In the face of a changing environment and cataclysmic events such as ecological disasters, variants that once were protective may become deleterious. Ongoing microevolutionary processes lead to transformations in the genetic architecture of adapting populations [2]
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