East London Genes & Health: human knockouts in a population genomic medicine cohort of British-South Asians (360G-Wellcome-210561_Z_18_Z)

East London Genes & Health is a long term programme for population genomic medicine research in British-South Asian adults. Unique features include high rates of health deprivation, especially diabetes, cardiovascular disease and mental health; high rates of consanguinity (including human knockouts, rare predicted loss of function variants occurring as homozygotes); local excellence in e-health record access/analysis; and recall for further research by genotype/phenotype. In this proposal we wish to continue and expand successful East London Genes & Health recruitment and commence a new site Bradford Genes & Health - to reach 100,000 volunteers; add value to the Genes & Health resource through SNP array genotyping all samples; and by sequencing and analysing consanguineous individuals. This will then enable us as a collaborative team to ask detailed research questions about adult-human knockouts. Specifically we will perform population based analyses of naturally occurring adult-human knockouts to better understand their population genetics, and (with Deciphering Developmental Disorders) recessive disease; contribute to and establish The Human Knockout Project, a worldwide database of population-based studies of human knockouts; perform blood -omics to study major perturbations of biological systems including downstream networks; and deeply study individuals with knockouts and other variants in reported Mendelian disease genes.