SELECTION OF POLYMORPHIC LOCI FOR ASSOCIATION ANALYSIS IN GENETIC-EPIDEMIOLOGICAL STUDIES
Background. The study of the role of hereditary factors in the formation of multifactorial signs is relevant, and in relation to multifactorial diseases, these studies are important for medicine. When planning genetic and epidemiological studies of multifactorial signs (diseases), it is important to select polymorphic loci to find associations with the studied phenotype (disease). The aim of the study. To carry out a systematic analysis of the data available in the modern literature on the approaches to the selection of polymorphic loci in the course of associative studies. Materials and methods. The review includes the current data of foreign and domestic articles on this topic found in Pubmed. Results. According to modern concepts, the selection of polymorphic loci of candidate genes to explore associations with a multifactorial trait (disease) requires the following criteria: 1) the presence of the association with the studied trait on the results of previously conducted genome-wide association (GWAS) and/or associative (i.e. replication) of research; 2) the presence of associations with phenotypes possessing common biological pathways with the studied trait; 3) regulatory capacity (regSNP); 4) influence on gene expression (eSNP); 5) association with nonsynonymous substitutions (nsSNP); 6) tagger SNP (tagSNP) 7) polymorphism frequency no less than 5% 8) functional effects (regSNP, eSNP, nsSNP) of SNPs in non-equilibrium by coupling (r2≥0.8) with polymorphisms selected for association analysis. The paper presents the characteristics of modern world databases on functional genomics and bioinformatics analysis methods used for in silico analysis of regulatory and eqtl SNPs values, evaluation of their block structure (SIFT, PolyPhen-2, HaploReg, rSNPs MAPPER, RegulomeDB, rSNPBase, SNP FuncPred, Blood eQTL browser, GTExportal, HaploView, LD TAG SNP Selection). Conclusion. The selection of polymorphic loci for associative studies should take into account their association with the studied feature according to the previous studies, the regulatory potential and the effect on gene expression, nsSNP and tagSNP, population frequency of at least 5%, and the functional effects of strongly coupled SNPs.
Ponomarenko IV. Selection of polymorphic loci for association analysis in genetic-epidemiological studies. Research Result. Medicine and Pharmacy. 2018;4(2):40-54 (In Russian)].
DOI: 10.18413/2313-8955-2018-4-2-0-5
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