Seven new publications out today describe the gnomAD resource and applications

We are delighted that the flagship publications describing the Genome Aggregation database (nomAD) have appeared today in Nature, Nature Medicine, and Nature Communications.Members of the CV Genetics & Genomics team have been long-term contributors to the gnomAD resource (and its predecessor, the exome aggregation consortium ExAC), and we have hugely enjoyed being part of this collaboration.Today’s package of publications includes two papers led by members of our team. “Characterising the loss-of-function impact of 5′ untranslated region variants in 15,708 individuals” has already been described in a previous blog post when we made our paper open access on the bioRxiv preprint server a year ago (see here), and leverages the power of gnomAD to annotate a particular group of variants that can cause severe rare genetic diseases. Rather than disrupting the sequence of the gene itself, these variants lie just upstream of the gene and interfere with regulatory signals that control translation of genes into proteins. This study was a home-grown effort, spear-headed by Nicky Whiffin while working at Imperial. The second study was also co-led by Nicky, and arose from a visit to spend some time working with Daniel MacArthur’s team at the Broad Institute. “The effect of LRRK2 loss-of-function variants in humans looks at a specific gene, LRRK2, suggested as a therapeutic target for Parkinson’s disease. There have been some concerns about the safety of targeting LRRK2 with drugs. However, Nicky and colleagues, working with data from gnomAD, 23andMe, and UK Biobank, found that individuals who carried genetic variants that inactivate one copy of this gene did not have any apparent adverse consequences. This provides reassurance that therapeutic inhibition of LRRK2 is likely to be well-tolerated and safe.You can read Nicky’s reflections on her work and the gnomAD package on her blog on her new webpage, which she has recently launched as she prepares to move to Oxford to set up a new lab at the Wellcome Centre for Human Genetics.

Post by James Ware