Approved Research

Genetic modifiers for metabolic traits.

Lay summary

Genetic modifiers or disease suppressors are genes that have the potential to counteract the effect of a disease-causing gene. They can explain why some people with genetic mutations linked to severe disease end up having only mild or no symptoms. Genetic modifiers could therefore positively influence the severity of disease and act as a 'natural form of protection'. Genetic modifier or suppressor genes are complex to identify with solely the use of population genetics, especially for rare genetic disorders. Furthermore, data from population genetics alone does not provide direct insight into the underlying biological process that causes disease suppression. Scenic Biotech has overcome the technical challenges of reliably finding genetic modifiers or the "hidden disease protection factors" using Cell-Seq, its large-scale pioneering human cell genetics platform (https://scenicbiotech.com).

We (Scenic Biotech) have the aim to identify genetic modifiers for disease genes of rare metabolic diseases such as Niemann-Pick type C and Barth syndrome using the Cell-Seq platform. Currently, no transformative treatment is available for these diseases. We have identified candidate genetic modifiers for various rare metabolic disorders that could potentially be pursued for target and drug development. In particular, Scenic aims to identify high confidence druggable modifiers that affect metabolic pathways relevant to the query diseases. To aid in the prioritization of these candidate targets, it would be of high value to evaluate these for their genetic association to disease traits in the UKB cohort. Targets are twice as likely to succeed in a clinical trial when it has population-genetics-based evidence to support its role in the disease. We therefore anticipate that our genetic analyses with the UK Biobank data will deepen our understanding of disease biology and the relevant target(s) to pursue, which can facilitate and accelerate novel drug development. This would be of high value to the patients awaiting valuable treatments for their conditions.