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In the UK10K project we propose a series of complementary genetic approaches to find new low frequency/rare variants contributing to disease phenotypes. These will be based on obtaining the genome wide sequence of 4000 samples from the TwinsUK and ALSPAC cohorts (at 6x sequence coverage), and the exome sequence (protein coding regions and related conserved sequence) of 6000 samples selected for extreme phenotypes. Our studies will focus primarily on cardiovascular-related quantitative traits, obesity and related metabolic traits, neurodevelopmental disorders and a limited number of extreme clinical phenotypes that will provide proof-of-concept for future familial trait sequencing. We will analyse directly quantitative traits in the cohorts and the selected traits in the extreme samples, and also use imputation down to 0.1% allele frequency to extend the analyses to further sample sets with genome wide genotype data. In each case we will investigate indels and larger structural variants as well as SNPs, and use statistical methods that combine rare variants in a locus or pathway as well as single-variant approaches.The SCOOP samples are part of the Obesity group and will undergo exome sequencing. Severe Childhood Onset Obesity Project (SCOOP) is a sub-cohort of the Genetics Of Obesity Study (GOOS) cohort established by Sadaf Farooqi and Steve O’Rahilly at the University of Cambridge over the last 12 years. The GOOS cohort contains >4,000 patients of diverse geographic origin, many of whom have monogenic and syndromic forms of obesity, and includes patients that are offspring of consanguineous union. SCOOP is a subset of >1500 UK Caucasian patients with severe, early onset obesity (all patients have a BMI Standard Deviation Score (SDS) > 3 and obesity onset before the age of 10 years), in whom all known monogenic causes of obesity have been excluded. GWAS data on the SCOOP cohort will be available (WTCCC2 independent study) at the time of the start of this study. Data from this cohort has demonstrated that the prevalence of the common obesity risk alleles in FTO, MC4R and NEGR1 are amongst the highest within SCOOP, demonstrating its value also in the study of genetic variants with an impact on more common obesity. For further information with regard to this cohort please contact Sadaf Farooqi (

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001000151 Illumina HiSeq 2000 88
EGAD00001000181 Illumina HiSeq 2000 212
EGAD00001000193 Illumina HiSeq 2000 573
EGAD00001000241 Illumina HiSeq 2000 674
EGAD00001000336 Illumina HiSeq 2000 784
EGAD00001000432 Illumina HiSeq 2000 985
EGAD00001000756 Illumina HiSeq 2000 1
EGAD00001001456 1
Publications Citations
The UK10K project identifies rare variants in health and disease.
Nature 526: 2015 82-90
ProxECAT: Proxy External Controls Association Test. A new case-control gene region association test using allele frequencies from public controls.
PLoS Genet 14: 2018 e1007591
Exome Sequencing Identifies Genes and Gene Sets Contributing to Severe Childhood Obesity, Linking PHIP Variants to Repressed POMC Transcription.
Cell Metab 31: 2020 1107-1119.e12
Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.
PLoS Biol 19: 2021 e3001255
Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.
Nat Med 28: 2022 2537-2546
A rare human variant that disrupts GPR10 signalling causes weight gain in mice.
Nat Commun 14: 2023 1450
Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.
Nat Genet 56: 2024 579-584