Polympact: exploring functional relations among common human genetic variants

Abstract

In the last years, many studies were able to identify associations between common genetic variants and complex diseases. However, the mechanistic biological links explaining these associations are still mostly unknown. Common variants are usually associated with a relatively small effect size, suggesting that interactions among multiple variants might be a major genetic component of complex diseases. Hence, elucidating the presence of functional relations among variants may be fundamental to identify putative variants’ interactions. To this aim, we developed Polympact, a web-based resource that allows to explore functional relations among human common variants by exploiting variants’ functional element landscape, their impact on transcription factor binding motifs, and their effect on transcript levels of protein-coding genes. Polympact characterizes over 18 million common variants and allows to explore putative relations by combining clustering analysis and innovative similarity and interaction network models. The properties of the network models were studied and the utility of Polympact was demonstrated by analysing the rich sets of Breast Cancer and Alzheimer's GWAS variants. We identified relations among multiple variants, suggesting putative interactions. Polympact is freely available at bcglab.cibio.unitn.it/polympact.

Analysis of Genetic Ancestry from NGS Data Using EthSEQ

“…(2020), the EthSEQ approach was extended to exploit three PCA dimensions instead of two, improving its sensitivity and precision. In addition, due to its application across different scenarios (Beltran et al., 2015; Gandellini et al., 2019; Huang et al., 2017; Orlando et al., 2022; Sailer et al., 2019; Valentini et al., 2022), several computational and reporting improvements have been implemented. Specifically, EthSEQ version 3 requires 10 times less memory and provides a much larger collection of reference models across different human reference genome assemblies.…”