Search of natural selection signals in genomic loci associated with diseases leading to impairment of human cognitive functions in Northern Eurasia populations

In recent years, the genetic component of many general common diseases has been considered from the point of view of evolutionary context: asthma, chronic obstructive pulmonary disease, cancer, obesity, diabetes. The genetic history of populations leads to the accumulation of specific frequencies. Modern susceptibility to common pathological phenotypes could have had a certain adaptive significance in the past during the dispersal of humans across the globe. Of particular interest are diseases with phenotypes associated with cognitive impairment, such as schizophrenia, Alzheimer's disease, bipolar disorder, autism and others. Diseases associated with post-reproductive age (various types of dementia), as well as various manifestations of psychotic disorders, which were previously uncommon, are currently acquiring enormous socioeconomic significance throughout the world. Evolutionary hypotheses have also been proposed for schizophrenia and Alzheimer's disease. The indigenous ethnic groups of Northern Eurasia are of particular interest to the researcher. Until recently, populations were isolated, isolated both by geography of residence and by linguistic and cultural characteristics, which led to genetic isolation. In this regard, the gene pool of populations of Northern Eurasia is an important source of genetic information. In connection with all of the above, the goal of the work was to search for signals of natural selection in the loci of the genome associated with schizophrenia, Alzheimer's disease, in the populations of Northern Eurasia. In our work, a search was performed for signals of natural selection in the loci of the genome associated with diseases leading to cognitive impairment in humans in 16 populations of Northern Eurasia: Russians, Udmurts, Khanty, Khakasses, northern and southern Kyrgyz, Yakuts, Buryats, Nivkhs, Chukchi, Kazakhs, Uzbeks, Altaians, Yakuts, Tuvins. MALDI-TOF mass spectrometry technology (Matrix Assisted Laser Desorption/Ionization Time Of Flight Mass-Spectrometry) was used for multiplex genotyping of 28 SNP markers. In our work, when analyzing selective neutrality using the Ewens-Watterson neutrality test for 28 markers, deviation from neutrality was found in 10 SNPs: rs10273775 of the CNTNAP2 gene, rs1031381 of the NCAPD3 gene, rs12922317 of the SNX29 gene, rs1466662 of the DCHS2 gene, rs1532278 of the CLU gene, rs16887244 of the LSM1 gene, rs3826656 of the CD33 gene, rs433598 of the ACSM1 gene, rs561655 near the PICALM gene, rs6859 of the NECTIN2 gene. The maximum number of populations for markers that have a deviation from selective neutrality was found for the genetic locus rs1031381 of the NCAPD3 gene - 10 populations (southern Kyrgyz, Altaians, Buryats, Koryaks, Tuvins, Khanty, Kazakhs, Udmurts, Kets, Uzbeks), while the minimum number of populations was identified for the marker rs16887244 of the LSM1 gene - one population (Nivkhs). In the present study, signals of natural selection were detected in all 16 populations. Interestingly, for the populations of northern Kyrgyz, Buryats, Koryaks, Khakasses and Udmurts, the effect of selection was only directional, and for the Russian population, the effect of balancing selection was noted, in the remaining ten populations, the effect of two types of selection was shown. For individual markers, only balancing selection was observed (rs16887244 of the LSM1 gene), while exclusively directional selection was detected for rs1466662 of the DCHS2 gene and rs561655 near the PICALM gene. It should be noted that of all 10 polymorphic variants of genes that showed deviation from selective neutrality, six SNPs showed statistically significant associations with schizophrenia or Alzheimer's disease in our previous studies in association analysis: rs12922317 of the SNX29 gene, rs1466662 of the DCHS2 gene, rs1532278 of the CLU gene, rs16887244 of the LSM1 gene, rs561655 near the PICALM gene, rs6859 of the NECTIN2 gene. The results of our work indicate a significant role of natural selection in the populations of Northern Eurasia in the formation of genetic diversity in the genes of diseases associated with human cognitive impairment, such as schizophrenia and Alzheimer's disease. The Authors declare no conflict of interest.