Strength in numbers in the low-frequency spectrum

Access through your institution Buy or subscribe The UK10K project was designed in two parts. The cohort part was intended to reveal the contribution of genetic variation to a range of 64

traits in 3,781 healthy individuals; this cohort was subjected to 7×, low-read-depth WGS. The other part of the project focused on exomes in some 6,000 individuals and, by high-read-depth

sequencing (80×), aimed to identify causal variants involved in rare disease, severe obesity and neurodevelopmental disorders. The main paper by the UK10K consortium provides an overview of

the project's strategy and findings, whereas other papers focus on associations between genetic variants and specific traits: Zheng _et al_. for bone mineral density and fracture;

Taylor _et al_. on thyroid function; and Timpson _et al_. for circulating lipid levels. Additionally, Geihs _et al_. describe web tools for accessing the association results and genome-wide

summary statistics, and the individual-level genotype and phenotype data are available under managed access conditions from UK10K Data Access. A project of this size and complexity is

certain to yield a plethora of useful insights, some of which are specific to individual traits, whereas others have broader implications. For example, the study revealed that the penetrance

of recognized variants for specific disorders — that is, the proportion of individuals harbouring a genetic variant that are affected by the associated phenotypic disorder — is likely to be

overestimated in many studies. The consortium authors suggest that, as a benchmark, future studies should also report estimates of population frequencies for a given reported variant. This

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during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * UK10K Consortium. The UK10K project

identifies rare variants in health and disease. _Nature_ http://www.dx.doi.org/10.1038/nature14962 (2015) * Zheng, H. F. et al. Whole-genome sequencing identifies _EN1_ as a determinant of

bone density and fracture. _Nature_ http://www.dx.doi.org/10.1038/nature14878 (2015) * Taylor, P. N. et al. Whole-genome sequence-based analysis of thyroid function. _Nat. Commun._ 6, 5681

(2015) Article  CAS  PubMed  PubMed Central  Google Scholar  * Timpson, N. J. et al. A rare variant in _APOC3_ is associated with plasma triglyceride and VLDL levels in Europeans. _Nat.

Commun._ 5, 4871 (2014) Article  CAS  PubMed  PubMed Central  Google Scholar  * Geihs, M. et al. An interactive genome browser of association results from the UK10K cohorts project.

_Bioinformatics_ http://dx.doi.org/10.1093/bioinformatics/btv491 (2015) * Huang, J. et al. Improved imputation of low-frequency and rare variants using the UK10K haplotype reference panel.

_Nat. Commun._ 6, 8111 (2015) Article  CAS  PubMed  PubMed Central  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Partner Journals, Magdalena

Skipper Authors * Magdalena Skipper View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE

CITE THIS ARTICLE Skipper, M. Strength in numbers in the low-frequency spectrum. _Nat Rev Genet_ 16, 623 (2015). https://doi.org/10.1038/nrg4024 Download citation * Published: 07 October

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