The Genetics of Extreme Blood Indices by Whole Genome Sequencing
Principal Investigator: Dr William Astle
Approved Research ID: 9616
Approval date: January 1st 2016
We are interested in the association between variants in our DNA code and blood cell indices. An analysis of the blood indices of the UK Biobank volunteers shows measurements for some individuals that are outside the normal ranges. We propose to analyse the whole genome sequence of these volunteers to better understand the reasons for this, including any interplay between the genetic code and the environment. This proposal is important because the elevation of certain blood indices is a risk factor for heart attack whilst an insufficient number of red blood cells is a frequent reason people visit their GP. The replenishment of blood cells by the stem cell is fundamental to human biology. Our genomics studies have thus far identified over 140 genetic loci that influence blood cell formation. Two thirds of these were novel associations. We propose to initiate whole genome sequencing of UK Biobank volunteers by selecting up to 2000 volunteers with extreme blood cell indices in order to identify rare genomic variants with large effect sizes. The proposed study complements our currently ongoing genomics studies in population samples and in individuals with inherited disorders of the blood. We have identified UK Biobank volunteers with extreme platelet and red cell indices. We will integrate environmental covariates, including lifestyle information, with blood cell measurements to identify volunteers who, with high likelihood, have outlier platelet or red cell indices due to intrinsic characteristics of their stem cells. We will whole genome sequence DNA samples from these individuals at Illumina Cambridge Ltd. We have a fifteen-member statistical and computational biology team at Cambridge University Hospitals and the Sanger Institute to perform association analyses and integrate the results of these analyses with the results from our other blood cell genomics studies. Genomics England Ltd and the NIHR BioResource ? Rare Diseases have secured an agreement with Illumina Cambridge Ltd for WGS analysis. Funds have been identified to WGS analyse up to 2000 UK Biobank volunteers.