A large-scale genome project into rare genetic variants has made “important new contributions” to understanding of disease and its risk factors, researchers report today.
The UK10K study examined almost 10,000 people, some of whom were healthy and others who had diseases or conditions such as schizophrenia, autism or rare disorders.
Researchers say by studying 64 different biomedical risk factors such as blood pressure or cholesterol levels among the healthy cohort they have gained valuable insight into the contribution of rare variants to a broad range of diseases.
They have also discovered new genetic variants and genes that underpin disease risk.
Dr Nicole Soranzo, corresponding author from the Wellcome Trust Sanger Institute, said the project had made important new contributions towards describing the role of rare genetic variants in a broad range of disease scenarios and human traits.
“It has shown that the value of sequencing a few thousand individuals is high for highly penetrant, rare diseases, but that for complex traits and diseases much larger sample sizes will be required in future studies,” she said. “The data and results produced by this project will be instrumental for these future efforts.”
This largest population genome sequencing project is published Nature, while a series of papers describing resources and application of the data is published at the same time in Nature, Nature Genetics, and Nature Communications.
The authors have also developed a web-based browser of association based on the Dalliance platform. Writing in Bioinformatics, they describe how this genome browser allows the easy retrieval of association results for all disease risk traits analysed in the study.
Scientists investigating specific disease risk factors will be able to access the consequence of a person’s DNA sequence to see how common any genetic variants they have are and what traits these variations are associated with.
The data and results of the UK10K study are expected to provide the foundation for the next wave of discoveries.
“The UK10K project was an enormous undertaking and has laid the ground for future studies,” said Klaudia Walter, a leading author from the Sanger Institute.
“For instance, the benefits of the new UK10K haplotype reference panel are already being realised in analyses of international consortia as well as the 0.5M people UK BioBank study.”
The UK10K Consortium (2015). The UK10K project identifies rare variants in health and disease. Nature 15 September 2015; doi: 10.1038/nature14962
Zheng H, Forgetta V et al. (2015). Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. Nature 15 September 2015; doi: 10.1038/nature14878
Huang J, Howie B, et al. (2015). Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel. Nature Communications 15 September 2015; doi: 10.1038/ncomms9111
Geihs M, Yan Y, et al. (2015). An interactive genome browser of association results from the UK10K cohorts project. Bioinformatics 15 September 2015; doi: 10.1093/bioinformatics/btv491
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