The GWAS-MAP platform for aggregation of results of genome-wide association studies and the GWAS-MAP|homo database of 70 billion genetic associations of human traits

Abstract

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.

Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging

“…Testing the 6 aging-related traits in the main cluster for correlations with 728 other traits from the GWAS-MAP platform 20 , we find that their genetic similarity may be largely explained through strong, shared genetic correlations (meta |r g | ≥ 0.5, false discovery rate (FDR) < 0.05, P het > 0.05, I 2 < 0.50) with chest pain, cardiovascular disorders, smoking-related disease, type 2 diabetes, and general illness or medication use in UK Biobank (Supplementary Data 2). However, each core aging trait also has several genetic correlations that differ substantially (Methods) from the other agingrelated phenotypes and may reflect population-or trait-specific risk factors.…”

“…Paul R. H. J. Timmers 1,2 ✉ , Evgeny S. Tiys 3,4 , Saori Sakaue 5,6,7,8 , Masato Akiyama 9,10 , Tuomo T. J. Kiiskinen 8,11 , Wei Zhou 8,12,13 , Shih-Jen Hwang 14,15 , Chen Yao 14,15 , Biobank Japan Project*, FinnGen*, Joris Deelen 16,17 , Daniel Levy 14,15 , Andrea Ganna 8,11,12 , Yoichiro Kamatani 9,18 , Yukinori Okada 6 , Peter K. Joshi 2 , James F. Wilson 1,2,20 and Yakov A. Tsepilov 3,19,20 Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits-healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health-in a principal component framework that maximizes their shared genetic architecture.…”

“…The number of SNPs used for this calculation is reported in Supplementary Data 1. LD-score (LDSC) regression 64 v.1.0.0 was used to calculate genetic correlations between selected GWAS summary statistics from the GWAS-MAP platform 20 and the aging-related GWAS and aging-GIP summary statistics used in our study, where the longer computation time of the HDL software would have been impractical. The GWAS-MAP platform contains summary statistics for 1,329,912 complex traits and gene expression levels, and 3,642 binary traits, derived from UK Biobank 62,65 and large European-ancestry consortia (for example, MAGIC, CARDIoGRAM, SSGAC and GIANT; for an up-to-date list of phenotypes, see https://phelige.com) 66 .…”

The GWAS-MAP|ovis platform for aggregation and analysis of genome-wide association study results in sheep

“…The GWAS-MAP platform (Shashkova, 2020;Shashkova, Aulchenko, 2020) to store GWAS results in the human was used as a basis to design the solution in question. For presentation and visualization of genetic data, the PheLiGe web interface was introduced (Shashkova et al, 2021).…”

“…In the field of human genetics, such a platform, known as GWAS-MAP (Shashkova et al, 2020), serves for unification, storing and analysis of millions of associations for thousands of human traits. However, to our knowledge, there is still no such a solution even for a single kind of livestock farming.…”