Publications by authors named "Gulnara Svishcheva"

Introduction: Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.

Objectives: We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.

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Gene-based association analysis is a powerful tool for identifying genes that explain trait variability. An essential step of this analysis is a conditional analysis. It aims to eliminate the influence of SNPs outside the gene, which are in linkage disequilibrium with intragenic SNPs.

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Back pain (BP) is a major contributor to disability worldwide, with heritability estimated at 40-60%. However, less than half of the heritability is explained by common genetic variants identified by genome-wide association studies. More powerful methods and rare and ultra-rare variant analysis may offer additional insight.

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Every week, 1-2 breeds of farm animals, including local cattle, disappear in the world. As the keepers of rare allelic variants, native breeds potentially expand the range of genetic solutions to possible problems of the future, which means that the study of the genetic structure of these breeds is an urgent task. Providing nomadic herders with valuable resources necessary for life, domestic yaks have also become an important object of study.

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We propose a novel effective framework for the analysis of the shared genetic background for a set of genetically correlated traits using SNP-level GWAS summary statistics. This framework called SHAHER is based on the construction of a linear combination of traits by maximizing the proportion of its genetic variance explained by the shared genetic factors. SHAHER requires only full GWAS summary statistics and matrices of genetic and phenotypic correlations between traits as inputs.

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Gene-based association analysis is an effective gene-mapping tool. Many gene-based methods have been proposed recently. However, their power depends on the underlying genetic architecture, which is rarely known in complex traits, and so it is likely that a combination of such methods could serve as a universal approach.

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Mongolian goats are of great interest for studying ancient migration routes and domestication, and also represent a good model of adaptability to harsh environments. Recent climatic disasters and uncontrolled massive breeding endangered the valuable genetic resources of Mongolian goats and raised the question of their conservation status. Meanwhile, Mongolian goats have never been studied on genomic scale.

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We report the genetic analysis of 18 population samples of animals, which were taken from cattle () breeds of European and Asian origins. The main strength of our study is the use of rare and ancient native cattle breeds: the Altai, Ukrainian Grey, Tagil, and Buryat ones. The cattle samples studied have different production purposes, belong to various eco-geographic regions, and consequently have distinct farming conditions.

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Article Synopsis
  • A new flexible model has been developed to analyze the relationship between genetic variants and traits without needing original individual-level genetic and phenotype data, relying instead on summary statistics.
  • This model builds on classical multiple linear regression methods but incorporates SNP-by-SNP correlations as explanatory variables and summary Z score statistics as response variables.
  • The proposed model produces identical results to traditional regional association analysis methods when using the same genetic data, ensuring no loss of information.
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  • A large amount of genome-wide association studies (GWAS) summary statistics can be used to identify rare genetic variants, but few existing methods are geared for this type of data.
  • Researchers have modified popular gene-based association analysis methods to work with GWAS summary statistics, implementing these changes in the R package called sumFREGAT.
  • The new package has been tested using data on coronary artery disease and successfully identified genes that previous methods did not detect, and it is available for free online.
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  • Functional linear regression models are useful for gene-based analysis of complex traits by integrating genetic variant information and minimizing noise.
  • * The introduction of allele-specific weights enhances the analysis by prioritizing more informative genetic components, potentially increasing the power of detection.
  • * In a study using real blood pressure data, the weighted models showed better association with certain genes, demonstrating improved results compared to unweighted models; the new method is available in the FREGAT package.
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Background: Despite high heritability, little success was achieved in mapping genetic determinants of depression-related traits by means of genome-wide association studies.

Methods: To identify genes associated with depressive symptomology, we performed a gene-based association analysis of nonsynonymous variation captured using exome-sequencing and exome-chip genotyping in a genetically isolated population from the Netherlands (n = 1999). Finally, we reproduced our significant findings in an independent population-based cohort (n = 1604).

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Article Synopsis
  • FREGAT is an R package designed for region-based association analysis of quantitative traits, suitable for both family and population samples.
  • It incorporates various methods, such as burden tests and kernel machine-based regression, making it versatile for genome/exome-wide studies and candidate gene analysis.
  • The package is available online, along with supplementary data, and aims to enhance the effectiveness and applicability of association analyses.
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Article Synopsis
  • * The new method, an extension of functional data analysis for related individuals, incorporates random polygene effects and shows improved statistical power over traditional burden-based and kernel-based methods across various scenarios.
  • * Implemented in the R-function 'famFLM', the method uses B-spline and Fourier basis functions, with Fourier models showing superior speed and power, and is freely available under GPLv3 at the specified URL.
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  • The FFBSKAT is a new R package designed for fast analysis of rare genetic variants in related individuals, particularly for quantitative traits.
  • It uses a score-based variance component test to connect single nucleotide polymorphisms (SNPs) with continuous traits, significantly speeding up calculations compared to current methods like ASKAT and famSKAT.
  • FFBSKAT combines features from these existing tools while adding new options, making it user-friendly and effective for researchers in genetics, and it’s available for free download online.
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Article Synopsis
  • Regional association analysis improves gene mapping for rare genetic variants in genome-wide studies by analyzing groups of SNPs rather than testing each one individually.
  • A novel kernel machine-based regression approach is proposed to enhance the accuracy of these analyses, particularly for related individuals, which previous methods did not adequately address.
  • The study shows that using the GRAMMAR+ transformation leads to better performance and fewer errors in association testing compared to other methods, making it a valuable tool for analyzing genetic data in related samples with existing software.
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The variance component tests used in genome-wide association studies (GWAS) including large sample sizes become computationally exhaustive when the number of genetic markers is over a few hundred thousand. We present an extremely fast variance components-based two-step method, GRAMMAR-Gamma, developed as an analytical approximation within a framework of the score test approach. Using simulated and real human GWAS data sets, we show that this method provides unbiased estimates of the SNP effect and has a power close to that of the likelihood ratio test-based method.

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