BACKGROUND Exposure to life-threatening events is common and everyone will most likely experience this type of trauma during their lifetime. Reactions to these events are highly heterogeneous and seems to be influenced by genes as well. Some individuals will develop posttraumatic stress disorder (PTSD), while others will not. In this study, our aim was to analyze the correlation between single nucleotide polymorphisms (SNPs) within the oxytocin receptor (OXTR) gene (rs53576 and rs2254298), the RAR-related orphan receptor A (RORA) gene (rs8042149) and the cannabinoid receptor 1 (CNR1) gene (rs1049353) and PTSD. All candidate genes have been previously associated with stress related disorders and the reaction to traumatic events. SUBJECTS AND METHODS Participants (N=719) have been exposed to war-related trauma during the war in South-Eastern Europe (Bosnia and Herzegovina, Croatia and Kosovo). We correlated the presence and absence of current and lifetime PTSD as well as PTSD severity (Clinician Administered PTSD scale (CAPS)) and current psychopathology (Brief Symptom Inventory (BSI) score) with the mentioned SNPs. DNA was isolated from whole blood and genotyped for OXTR rs2254298 and rs53576 following previously published protocols, for RORA rs8042149 via PCR-RFLP and CNR1 rs1049353 via KASP. RESULTS Nominally significant results were found for OXTR rs53576 in connection with the CAPS and BSI scores within lifetime PTSD patients. The additive allelic model indicated that G allele carriers achieved lower CAPS (p=0.0090) and BSI (p=0.0408) scores than participants carrying one or two copies of the A allele. These results did not withstand correction for multiple tests. No significant results were observed for OXTR rs2254298, RORA rs8042149 and CNR1 rs1049353 although the results for RORA showed a slight tendency that rs8042149 may influence the level of BSI scores in current PTSD patients. CONCLUSIONS This study points to a role of the OXTR gene in PTSD and the related psychopathology following war related trauma.

BACKGROUND Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s. SUBJECTS AND METHODS This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay. RESULTS Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected. CONCLUSION We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.

BACKGROUND Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology. SUBJECTS AND METHODS 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology. RESULTS A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology. CONCLUSIONS Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.

Abstract Background: Serbs mainly live in the territory of the recently re-established state of Serbia. However, the turbulent history in the Balkan Peninsula has led to settlement of Serbs not only within present day Serbia, but also in different parts of neighbouring countries. Aim: To define polymorphisms of 23 Y-chromosomal short tandem repeat (STR) loci in a modern Serbian population from the central part of the Balkan Peninsula. Subjects and methods: The reference sample consisted of 303 men declared as Serbs over three generations. Localities of the collected materials include the territories of Serbia, Bosnia and Herzegovina, Croatia and Montenegro. DNA samples were typed using the PowerPlex®Y23 amplification kit. Results: The highest locus diversity was observed for DYS385 and DYS481. In this study the most abundant haplogroups were I2a, E1b1b, R1a and I1. The largest genetic distances between the Serbs and other close Southern Slavs were for the Macedonians and Slovenians. Conclusion: This study is the first one to define STR polymorphism of Serbian people not only from Serbia but also from other parts of the Balkan Peninsula. The presented genetic data may be useful in further examinations of the genesis and genetic structuring of the present-day Serbian gene pool.

Introduction: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. Aim: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. Results: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). Conclusions: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

Abstract The aim of this study is to provide an insight into Balkan populations’ genetic relations utilizing in silico analysis of Y-STR haplotypes and performing haplogroup predictions together with network analysis of the same haplotypes for visualization of the relations between chosen haplotypes and Balkan populations in general. The population dataset used in this study was obtained using 23, 17, 12, 9 and 7 Y-STR loci for 13 populations. The 13 populations include: Bosnia and Herzegovina (B&H), Croatia, Macedonia, Slovenia, Greece, Romany (Hungary), Hungary, Serbia, Montenegro, Albania, Kosovo, Romania and Bulgaria. The overall dataset contains a total of 2179 samples with 1878 different haplotypes. I2a was detected as the major haplogroup in four out of thirteen analysed Balkan populations. The four populations (B&H, Croatia, Montenegro and Serbia) which had I2a as the most prevalent haplogroup were all from the former Yugoslavian republic. The remaining two major populations from former Yugoslavia, Macedonia and Slovenia, had E1b1b and R1a haplogroups as the most prevalent, respectively. The populations with E1b1b haplogroup as the most prevalent one are Macedonian, Romanian, as well as Albanian populations from Kosovo and Albania. The I2a haplogroup cluster is more compact when compared to E1b1b and R1b haplogroup clusters, indicating a larger degree of homogeneity within the haplotypes that belong to the I2a haplogroup. Our study demonstrates that a combination of haplogroup prediction and network analysis represents an effective approach to utilize publicly available Y-STR datasets for population genetics.

Several association studies focusing on FTO gene polymorphisms have been published in the past years; however, the association between FTO -related conditions and FTO gene variants remains unexplained. Population genetics and association studies of different populations provide a valuable tool for further research. Thus, the aim of this systematic review is to summarize current knowledge on the FTO SNP rs9939609, and its association with presumably related conditions. The study included original research articles collected from PubMed and ResearchGate databases that were published in the period between 2007 and November 2017, and that provide information on rs9939609 mutant allele frequency and its probable association with any condition suspected of being related to the mutant allele. Genotype data was extracted and analyzed, and missing data was obtained from secondary sources. Short summaries of relevant studies from primary sources are organized in an overview table. The results of the systematic review suggest that mutant allele A is the most prevalent in European populations and least frequent on the Far East. In addition, it has been concluded that allele A is a good tool for the prediction of an increased risk of higher-than-normal BMI in a person carrying it, as well as that allele A should be further analyzed as a possible risk marker for type 2 diabetes mellitus and polycystic ovary syndrome development.

Since the introduction of the term low copy number DNA, also referred as low template DNA, touch DNA or trace DNA analysis, it has quickly become focal point of forensic DNA testing as well as other DNA based studies. Low template DNA (ltDNA) samples can be described as the samples which involve single source samples with template DNA in concentrations below 100 picograms (pg). Due to sensitivity of ltDNA samples to contamination, it is of great importance to optimize performance of the multiplex STR systems and existing protocols to increase chance of successful analysis. The main objective of this study was analysis of 20 challenging samples (skeletal remains, cigarette buts, chewing gum, poorly collected buccal swabs etc.) mostly low template DNA samples, preliminarily profiled by PowerPlex® 16 multiplex STR systems and additionally processed with new generation multiplex STR kit PowerPlex® Fusion. Sample isolation was done using a standard phenol-chloroform method for bone samples and DNeasy® Blood and Tissue Kit for other forensic samples. PowerPlex® 16 (PP16), multiplex STR system and PowerPlex® Fusion (PP Fusion) were used for co-amplification of 15 and 24 autosomal STR loci respectively. Results of this preliminary study suggest that PP Fusion primer set is better optimized for the analysis of ltDNA samples, and it is more robust regarding presence of the potential PCR inhibitors.

The region of Western Balkans has been inhabited since the Paleolithic era and was the route of the spread of farming from the Middle East to Europe during the Neolithic era. In the present study, Y-STR data from European populations have been used to construct median-joining networks. The study was performed using Whit Athey’s Haplogroup Predictor, Y Utility and Network 4 software packages to predict Y haplogroups, construct networks, perform clustering of closely related Y chromosomes and calculate time estimates between individual nodes. The results of the study imply that geographically close populations cluster together at both Balkan and European levels. It was observed that an elevated number of study populations and individual haplogroups increases the possibility that individuals of different ethnic background cluster within the same or neighboring clades of network. Subsequent time estimates, performed based on the mutation frequency between the ancestral node and its descendant nodes, revealed that I2a haplogroup within the Western Balkan region has the most compact clustering (age, estimated at 3109 years), followed by Hg E1b1b which has the second most compact clustering (4896 years). The obtained results are nonetheless in accordance with previously published research investigating the frequency of Y haplogroups based on Y-SNP variant frequencies, indicating that Western Balkan countries are mainly represented by I2a subclade (average for six countries 32.3%), followed by E1b1b and R1a (average for six countries of 21.5% and 17%, respectively).

This study compares the results obtained using two multiplex systems, PowerPlex® 16 System and PowerPlex® Fusion System, to evaluate the probability of a specific kinship relationship between the offspring of three pairs of identical twins, such as full kinship (siblings), first-degree relatives (first cousins) and half-siblings. Genomic DNA was isolated and amplified from buccal swab and selected short tandem repeat (STR) markers were detected. Electropherograms were generated and analyzed for all persons, using two multiplex systems. Paternity testing for every nine offspring of six examined couples was performed and in all cases the probability that the alleged father is the true father, was over 99.9999%. Kinship analyses were performed setting up two different hypotheses and calculating the likelihood ratio (LR) and kinship probability. Determining the degree of kinship between persons who were full siblings, likelihood ratio showed the highest values contrary to other two types of kinship. Kinship analyses between first cousins showed a higher probability that the examined persons are half-siblings, rather than they are first cousins. In most cases, the introduction of additional seven loci included in PowerPlex® Fusion System increased the values of average likelihood ratios. It is recommendable to use over 20 STR loci in complex kinship analyses.