The UK10K project represents one of the first large scale applications of next generation sequencing to population based epidemiological samples and the examination of complex phenotypes. The objectives of this work are to record whole genome sequence variation at and below 1% minor allele frequency, to provide an imputation reference and to use this, not only to provide a resource for the scientific community (both genotypes and phenotypes), but also to examine genetic associations across a spectrum of genetic variation.

The study is composed of two samples drawn from European population based epidemiological studies (The Avon Longitudinal Study of Parents and children and Twins UK) and forms a collection of nearly 4000 participants now with whole genome sequence data and phenotypes (along with complementary imputed internal replication data sets). A total of 1,990 individuals from TwinsUK and 2,040 individuals from ALSPAC were consented for sequencing. Variant sites and genotype likelihoods were called using samtools and genotypes were refined and phased using BEAGLE, with similar procedures to the 1000 Genomes Project.

In addition, both ALSPAC and TwinsUK consented to release phenotype data related to cardiovascular disease as a public resource for the association analyses. Twelve anthropometric traits including height, weight, BMI, waist-hip-ratio, waist-hip-ratio (BMIadj), waist circumference, waist circumference (BMIadj), hip circumference and hip circumference (BMI adj) and DXA measures (total fat mass, total lean mass and trunk fat mass) phenotypes were released. The association analyses for the anthropometric traits are currently reaching a critical phase for the singlepoint associations, and also for those more rare variants with analyses being undertaken using variant aggregation techniques such as SKAT. Consequently, we are following up possible avenues for unraveling the underlying molecular mechanism of the identified genetic associations. To this end, we are writing to seek a collaborative arrangement efforts to continue our analysis of both single point and rare variant associations using expression (already part of UK10K agreement) and methylation data.