Research using data collected from around 4,000 healthy people
in the UK has enabled scientists from UCL, the Wellcome Trust
Sanger Institute and the University of Bristol to identify a
rare genetic variant that dramatically reduces levels of certain
types of lipids in the blood.
The study is the first to emerge from the UK10K Project's cohort
of samples from the general public and demonstrates the power of
whole genome sequencing at scale.
"Until now it has only been possible to look for common variants
of small effect in large genome wide association studies," said Dr
Nicholas Timpson of the University of Bristol. "Thanks to the
quantity of data available through the UK10K Project and because of
the relatively large effect of this variant, we have been able to
find a rare genetic variant that has clinical relevance."
By looking at whole genome sequences from 4,000 people and
comparing this with data about their lipid levels, scientists
spotted an association between levels of lipids called
triglycerides and the presence of the APOC3 gene variant. The
research suggests that people with the rare change (approximately
0.2 per cent of the population carry this) typically have lower
levels of triglycerides, which (as shown elsewhere) is associated
with reduced risk of cardiovascular disease.
Two studies in the New England Journal of Medicine have recently
explored the role of this genetic variant through the examination
of APOC3 in a targeted approach, and through coding and analysing
only part of the genome. These studies give important context to
this finding as they also relate this change to heart disease.
"These three studies independently reporting this finding give
us confidence that it is reliable and informative for clinical
understanding," said Professor Steve Humphries, a British Heart
Foundation-funded senior author from University College London.
"Once we can understand the mechanism of the protective function
of this variant, we can try to use this information to develop
novel therapies to help those at risk of cardiovascular
disease."
This is the first in a series of studies that will use whole
genome sequences and clinical information about physical
characteristics from the UK10K project to find rare genetic
variants.
"Extending genome wide association studies to include whole
genome sequencing can help us to identify more clinically
informative variants," said Dr Nicole Soranzo of the Wellcome Trust
Sanger Institute. "Data collected as part of the UK10K project is
essential to this and we are beginning to see its extraordinary
value."
The paper, A rare variant in APOC3 is associated with plasma triglyceride and
VLDL levels in Europeans, is published in Nature
Communications.