The INTERVAL trial is a randomised trial assessing how often blood donors can safely give whole blood. In addition to questions that can be answered by the randomised trial, we have also created a bioresource of the 50,000 trial participants to address other epidemiological questions, particularly those relating to genetics.

In all participants, we have:

• collated basic lifestyle and self-reported health nformation using a web-based questionnaire;
• assayed a genome-wide genotyping array containing >800,000 genetic variants;
• imputed from this array backbone to >80 million variants;
• used a Sysmex haematology analyser to assay >50 blood cell parameters;
• assessed ~230 metabolites using a NMR platform covering lipoproteins, lipids and low molecular weight metabolites;

In subsets of participants, we have:

• conducted high-depth (50x) whole exome sequencing;
• conducted low-pass (15x) whole genome sequencing;
• measured thousands of soluble proteins using a novel aptamer-based assay approach;
• assayed >1000 metabolites using a mass-spectrometry platform;
• assayed >400 lipid species using a bespoke mass-spectrometry platform;
• measured candidate biomarkers of relevance to blood donation (eg, iron-related markers);
• assessed cognitive function using a validated four-domain online testing platform.

Examples of publications arising already from the INTERVAL bioresource include:

Genetic association studies

• Astle W, Elding H, Tao J et al., The allelic landscape of human blood cell trait variation and links to complex diseases. Cell 167, 1-15.

Studies using INTERVAL donors as healthy controls

• Sifrim A, Hitz MP, Wilsdon A et al., 2016. Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing. Nat Genet 48(9):1060-5.
• Singh T, Kurki MI, Curtis D et al., Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nat Neurosci 19(4):571-7.

Other uses of the INTERVAL bioresource include recall-by-genotype studies, including the subset of INTERVAL participants who have consented to join the NIHR Bioresource, trials nested within the INTERVAL bioresource, such as the INFORM trial, and studies involving new measurements, such as the nasal swabs of Staphylococcus aureus employed in the CARRIAGE study.