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
The heritability of borderline personality (BP) features has been established in multiple twin and family studies. Using data from the borderline subscale of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in two Dutch cohorts (N=7125), the Netherlands Twin Register and The Netherlands Study of Depression and Anxiety, we show that heritability of the PAI-BOR total score using genome-wide single-nucleotide polymorphism (SNPs) is estimated at 23%, and that the genetic variance is substantially higher in affect instability items compared with the other three subscales of the PAI-BOR (42.7% vs non-significant estimates for self-harm, negative relations and identity problems). We present results from a first genome-wide association study of BP features, which shows a promising signal on chromosome 5 corresponding to SERINC5, a protein involved in myelination. Reduced myelination has been suggested as possibly having a role in the development of psychiatric disorders characterized by lack of social interaction. The signal was confirmed in a third independent Dutch cohort drawn from the Erasmus Rucphen Family study (N=1301). Our analyses were complemented by investigating the heterogeneity that was implied by the differences in genetic variance components in the four subscales of the PAI-BOR. These analyses show that the association of SNPs tagging SERINC5 differs substantially across the 24 items of the PAI-BOR. Further, using reverse regression we showed that the effects were present only in subjects with higher scores on the PAI-BOR. Taken together, these results suggest that future genome-wide analyses can benefit substantially by taking into account the phenotypic and genetic heterogeneity of BP features.
