Science in focus: Genomic Lens study provides new insights into disease genetics

21 December 2023

As part of our second edition of our ´Science in focus´ series, we feature a recent publication¹ that analysed the impact of structural variants (SVs) on traits related to diseases such as idiopathic pulmonary fibrosis (IPF) and metabolic dysfunction-associated steatohepatitis (MASH). As part of this synopsis, we make key data of this article available through the opnMe portal to allow unrestricted access to researchers worldwide.

Establishing an association between a specific genetic modification and a defined disease phenotype represents an important step in the discovery of new drug targets. Drug target identification takes a lot of effort and requires many costly and time-consuming experiments. Hence, integrating computational methods and analyses of large-data population biobanks into target identification can significantly accelerate the discovery research process towards novel treatments for patients.

Researchers at Boehringer Ingelheim now have created a new “genomic lens” that helps scientists to speed up drug discovery at lower costs. The novelty of their approach is the incorporation of SVs into genome-wide association analyses (GWAS). Rather than sequencing whole genomes of participants of cohort studies, they sequenced a limited number of individuals to establish a high-quality SV reference panel. 888 individuals of different ancestries from the 1000 Genomes Project were sequenced with the Oxford Nanopore long-read platform that facilitates detection of SVs.

The team demonstrated the utility of the SV reference panel by imputing SVs into the approximately 500,000 participants of the UK Biobank and conducting GWASs on 32 disease-relevant traits and protein level data of 1,463 proteins. Thereby, they were able to identify causal genes at hundreds of associated loci, as highlighted with selected examples with direct relevance to respiratory diseases, such as IPF.

The authors concluded that use of SV imputation constitutes a practical and cost-effective solution for the robust analysis of common SVs. The multi-ancestry imputation panel applied in the present study to Europeans from UK Biobank can also be used to impute SVs in diverse ancestries, e.g., from BioBank Japan, China Kadoorie Biobank, or the Singapore Precision Medicine Program.

To facilitate wider impact of this well-characterized panel generated from the Genomic Lens project, the underlying data have been made available exclusively via the opnMe portal.

Significance of this study

The authors explained that the data will help to find novel associations between genetics and phenotypic traits. Ultimately, these associations will help to identify new drug targets or biomarkers. The study also highlights the value of using SVs to identify potential causal genes in loci with multiple candidate genes. The findings emphasize the potential of SVs in enhancing our understanding of genetic factors influencing complex diseases, and the incorporation of SVs in post-GWAS gene-prioritization approaches is anticipated to become standard practice.

It is our hope that making the panel available through opnMe will accelerate research on the genetic underpinnings of diverse diseases and facilitate the identification of novel therapeutic concepts.

About the Genomic lens study

The Genomic lens project is a collaboration between scientists from two Boehringer Ingelheim departments, the Global Computational Biology and Digital Sciences (gCBDS), and BI X, the Digital Lab of Boehringer Ingelheim.

1. Noyvert B., Erzurumluoglu A. M., Drichel D., Omland S., Andlauer T. F. M., Mueller S., Sennels L., Becker C., Kantorovich A., Brænne I., Bartholdy B. A., Belbin G. M., Li J. H., Pickrell J. K., de Jong J., Arora J., Kriegl J., Podduturi N., Jensen J. N., Stutzki J., Ding Z. Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations. medRxiv. 2023. DOI.

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About opnMe:

opnMe.com, the open science portal of Boehringer Ingelheim, aims to accelerate research initiatives to enable new insights of disease biology in areas of high unmet medical need by sharing well-characterized molecules and offer collaborations for science. In the spirit of collaboration, our molecules are provided to the scientific community to help unlock and fulfill their full potential. These molecules are either freely available as “Molecules to Order” or applied via scientific research submissions as “Molecules for Collaboration.” As part of our third pillar, our “opn2EXPERTS” program, we also enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs.

*Using the link to the Genomic Lens data will take you to a domain beyond the control of Boehringer Ingelheim. This link is provided for your convenience, and its inclusion does not imply Boehringer Ingelheim endorsement of the site.