FKBP51 is a key stress-responsive regulator of the hypothalamic–pituitary–adrenal axis. To elucidate the contribution of rs1360780 FKBP5 C/T alleles to aging and longevity, we genotyped FKBP5 in a cohort of 800 non-demented and Alzheimer’s disease (AD) subjects of different age, taking into account the allele state of ApoE ε4, the major risk factor for AD. Furthermore, we searched for the association of FKBP5 with subcohorts of non-demented subjects evaluated for anxiety and resting-state quantitative EEG characteristics, associated with cognitive, emotional, and functional brain activities. We observed that increased state anxiety scores depend on the combination of the FKBP5 and ApoE genotypes and on the DNA methylation state of the FKBP5 promoter and ApoE genotype. We also found a significant gender-dependent correlation between FKBP5 promoter methylation and alpha-, delta-, and theta-rhythms. Analysis of the FKBP5 expression in an independent cohort revealed a significant upregulation of FKBP5 in females versus males. Our data suggest a synergistic effect of the stress-associated (FKBP5) and neurodegeneration-associated (ApoE) gene alleles on anxiety and the gender-dependent effect of FKBP5 on neurophysiological brain activity.

The development of new biomarkers for prediction and early detection of human diseases, as well as for monitoring the response to therapy is one of the most relevant areas of modern human genetics and genomics. Until recently, it was believed that the function of human Y chromosome genes was limited to determining sex and controlling spermatogenesis. Thanks to occurance of large databases of the genome-wide association study (GWAS), there has been a transition to the use of large samples for analyzing genetic changes in both normal and pathological conditions. This has made it possible to assess the association of mosaic aneuploidy of the Y chromosome in somatic cells with a shorter lifespan in men compared to women. Based on data from the UK Biobank, an association was found between mosaic loss of the Y chromosome (mLOY) in peripheral blood leukocytes and the age of men over 70, as well as a number of oncological, cardiac, metabolic, neurodegenerative, and psychiatric diseases. As a result, mLOY in peripheral blood cells has been considered a potential marker of biological age in men and as a marker of certain age-related diseases. Currently, numerous associations have been identified between mLOY and genes based on GWAS and transcriptomes in affected tissues. However, the exact cause of mLOY and the impact and consequences of this phenomenon at the whole organism level have not been established. In particular, it is unclear whether aneuploidy of the Y chromosome in blood cells may affect the development of pathologies that manifest in other organs, such as the brain in Alzheimer’s disease, or whether it is a neutral biomarker of general genomic instability. This review examines the main pathologies and genetic factors associated with mLOY, as well as the hypotheses regarding their interplay. Special attention is given to recent studies on mLOY in brain cells in Alzheimer’s disease.

The clusterin (CLU) rs11136000 CC genotype is a probable risk factor for Alzheimer’s disease (AD). CLU, also known as the apolipoprotein J gene, shares certain properties with the apolipoprotein E (APOE) gene with a well-established relationship with AD. This study aimed to determine whether the electrophysiological patterns of brain activation during the letter fluency task (LFT) depend on CLU genotypes in adults without dementia. Previous studies have shown that LFT performance involves activation of the frontal cortex. We examined EEG alpha1 and alpha2 band desynchronization in the frontal regions during the LFT in 94 nondemented individuals stratified by CLU (rs11136000) genotype. Starting at 30 years of age, CLU CC carriers exhibited more pronounced task-related alpha2 desynchronization than CLU CT&TT carriers in the absence of any differences in LFT performance. In CLU CC carriers, alpha2 desynchronization was significantly correlated with age. Increased task-related activation in individuals at genetic risk for AD may reflect greater “effort” to perform the task and/or neuronal hyperexcitability. The results show that the CLU genotype is associated with neuronal hyperactivation in the frontal cortex during cognitive tasks performances in nondemented individuals, suggesting systematic vulnerability of LFT related cognitive networks in people carrying unfavorable CLU alleles.

The history of Ancient Rus’ is inextricably linked with the history of ancient Vladimir, the capital of North-Eastern Rus’ in the 12th–14th centuries. Historical, anthropological, and archaeological data suggest a complex composition of the population of Ancient Rus’ cities, however, the genetic structure of this population is currently practically unexplored. We performed whole-genome sequencing with high coverage for an individual from a burial with a stone pillow from the necropolis “Patriarch's Garden” in Vladimir, dated to the second half of the 13th–14th centuries. Based on this, the individual was identified as a male. Identified haplogroups of mitochondrial DNA (H1ba) and Y-chromosome (R-L21) of the buried man have not been previously described in burials from the territory of Ancient Rus’. The paternal lineage of the individual is likely traced to the territory of Northwest Europe. In combination with data on autosomal markers, these results testify to the genetic connection of the man buried in Vladimir with the Western European populations.

The foundation of the first ancient Rus′ state occurred as a result of the consolidation of diverse communities inhabiting Eastern Europe during the second half of the first millennium CE. Historical sources imply that these communities mostly include East Slavs, whose settlement across a vast territory led to the emergence of the East Slavic/Rus′ culture within the Rus′ state. We generated genomic data for 200 medieval individuals from different locations to elucidate the origin and genetic structure of the Rus′ population during the early stages of the state formation. Our findings reveal a genetic continuum predominantly shaped by two key genetic groups: a broad Slavic-related continuity of different genetic subclusters of Rus′ occupying the enormous European Plain area, and a Fenno-Ugrian (Uralic)-related component in the Northern Rus′ region. Importantly, both groups have a shared genetic substrate inherited from preceding ancient Baltic region populations. To scale Scandinavian ("Viking") heritage, we traced minor Scandinavian genetic lineages that did not make up the dominating genetic stratum of the early Rus′ state. Our study presents the first comprehensive genomic image of the medieval Rus′, highlighting the intricate cultural and genetic interactions between Slavic, Fenno-Ugrian, and other groups that formed the first Rus′ state affecting Europe's history.