RESUMO
Hundreds of genome-wide association studies (GWAS) of human traits are performed each year. The results of GWAS are often published in the form of summary statistics. Information from summary statistics can be used for multiple purposes - from fundamental research in biology and genetics to the search for potential biomarkers and therapeutic targets. While the amount of GWAS summary statistics collected by the scientific community is rapidly increasing, the use of this data is limited by the lack of generally accepted standards. In particular, the researchers who would like to use GWAS summary statistics in their studies have to become aware that the data are scattered across multiple websites, are presented in a variety of formats, and, often, were not quality controlled. Moreover, each available summary statistics analysis tools will ask for data to be presented in their own internal format. To address these issues, we developed GWAS-MAP, a high-throughput platform for aggregating, storing, analyzing, visualizing and providing access to a database of big data that result from region- and genome-wide association studies. The database currently contains information on more than 70 billion associations between genetic variants and human diseases, quantitative traits, and "omics" traits. The GWAS-MAP platform and database can be used for studying the etiology of human diseases, building predictive risk models and finding potential biomarkers and therapeutic interventions. In order to demonstrate a typical application of the platform as an approach for extracting new biological knowledge and establishing mechanistic hypotheses, we analyzed varicose veins, a disease affecting on average every third adult in Russia. The results of analysis confirmed known epidemiologic associations for this disease and led us to propose a hypothesis that increased levels of MICB and CD209 proteins in human plasma may increase susceptibility to varicose veins.
RESUMO
We studied the effects of single nucleotide polymorphisms in the promoter regions of matrix metalloproteinase genes rs1799750 (-1607dupG) MMP1, rs243865 (C-1306T) MMP2, rs3025058 (-1171dupA) MMP3, and rs11568818 (A-181G) MMP7 on the risk of varicose vein of the lower extremities in ethnical Russians, residents of the Russian Federation. We genotyped 536 patients with this pathology and 273 healthy participants without history of chronic venous disease. Association was examined using logistic regression analysis. None of the studied polymorphisms showed statistically significant association with the risk of varicose veins of the lower extremities. Our results provide evidence that these polymorphisms are not involved in the pathogenesis of varicose veins and cannot serve as markers of predisposition to this pathology.
Assuntos
Extremidade Inferior/patologia , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Varizes/epidemiologia , Varizes/genética , Adulto , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We analyzed associations between single nucleotide polymorphisms (SNP) rs13155212 and rs7704267 in the AGGF1 gene (angiogenic factor with G patch and FHA domains 1) and the risk of risk of varicose veins of the legs in ethnic Russians. Frequencies of alleles, genotypes, and haplotypes were estimated in the sample of patients with this disease (474 patients) and in the control group of participants (478 volunteers) without a history of chronic venous disease. None of the studied polymorphisms was associated with the risk of this pathology. The whole AGGF1 gene sequence lies in a single block of high linkage disequilibrium, and both studied polymorphic variants are representative of all other SNP within this region. From these results, a conclusion was made that AGGF1 gene polymorphism does not affect the risk of varicose veins of the legs in ethnic Russians, or its contribution is low and can be revealed only after analysis of larger cohorts.
Assuntos
Proteínas Angiogênicas/genética , Perna (Membro)/irrigação sanguínea , Varizes/genética , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Federação RussaRESUMO
The genetic polymorphism of enzymes of synthesis and metabolism of estrogens can input into predisposition to breast cancer. The purpose of actual study was to analyze the associations of polymorphic loci CYP17/B1rs10556836, CYP1A 1rs1048943, CYP1A2rs762551, CYP19A1rs2470152 and CYP17A1rs743572 with risk of development of breast cancer in Russian residents of the Western-Siberian region of Russia. The rates of alleles and genotypes of the given loci were determined in sampling of women suffering with breast cancer (n = 670 females) and in control group (480 females without oncological diseases). The sub-groups of patients with breast cancer in pre-menopause--and post-menopause were analyzed separately. The border-line association of locus CYP17A1rs743572 is demonstrated with increasing of risk of breast cancer during pre-menopause (allele C: p = 0.04). Among the rest of polymorphic loci no association was detected.
