Non-specific structural chromosomal aberrations (CAs) observed in peripheral blood lymphocytes of healthy individuals can be either chromosome-type aberrations (CSAs) or chromatid-type aberrations (CTAs) depending on the stage of cell division they are induced in and mechanism of formation. It is important to study the genetic basis of chromosomal instability as it is a marker of genotoxic exposure and a predictor of cancer risk. For that purpose, we conducted two genome-wide association studies (GWASs) on healthy individuals in the presence and absence of apparent genotoxic exposure from the Czech Republic and Slovakia. The pre-GWAS cytogenetic analysis reported the frequencies of CSA, CTA and total CA (CAtot). We performed both linear and binary logistic regression analysis with an arbitrary cut-off point of 2% for CAtot and 1% for CSA and CTA. Using the statistical threshold of 1.0 × 10-5, we identified five loci with in silico predicted functionality in the reference group and four loci in the exposed group, with no overlap between the associated regions. A meta-analysis on the two GWASs identified further four loci with moderate associations in each of the studies. From the reference group mainly loci within genes related to DNA damage response/repair were identified. Other loci identified from both the reference and exposed groups were found to be involved in the segregation of chromosomes and chromatin modification. Some of the discovered regions in each group were implicated in tumourigenesis and autism.

Biomedical Center Martin Jessenius Faculty of Medicine Comenius University in Bratislava Martin Slovakia

Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Pilsen Czech Republic

Department of Biology Faculty of Medicine Slovak Medical University Bratislava Slovakia

Department of Genomics Life and Brain Center University of Bonn Bonn Germany

Department of Medical Genetics 3rd Faculty of Medicine Charles University Prague Czech Republic

Department of Molecular Biology of Cancer Institute of Experimental Medicine Czech Academy of Sciences Prague Czech Republic

Department of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany

Department of Molecular Oncology Cancer Research Institute Biomedical Research Center Slovak Academy of Sciences Bratislava Slovakia

Division of Medical Genetics Department of Biomedicine University of Basel Basel Switzerland

Health Effects Laboratory Department of Environmental Chemistry NILU Norwegian Institute for Air Research Kjeller Norway

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Human Genetics University of Bonn Bonn Germany

Medizinische Fakultät Universität Heidelberg Heidelberg Germany

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DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations