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Approved research

Associations between the PER3 VNTR polymorphism and sleep, circadian, cognitive and health phenotypes in the UK Biobank WES data

Principal Investigator: Dr Simon Archer
Approved Research ID: 59619
Approval date: June 24th 2020

Lay summary

The circadian body clock regulates the daily temporal organisation of many of the body's 24h rhythms including metabolism, immune function, cell growth, cognition, and the sleep-wake cycle. PERIOD3 (PER3) is one of the genes that regulates the circadian clock. In studies with small numbers of participants (up to 675), we have found that a particular genetic variant within PER3 is associated with diurnal preference, sleep-wake timing, brain activity, light sensitivity, cognitive performance, and a clinical condition called delayed sleep phase disorder where people go to bed and get up very late. Other small-scale studies have also shown links with bipolar disorder, diabetes, schizophrenia, cancer and addiction. The aim of this project is to investigate in greater detail the potential links between this PER3 variant with a much wider range of health conditions in the large UK Biobank cohort of participants. The PER3 variant that we are interested in is a repeated section of DNA of up to 270 nucleotides (the individual building blocks of DNA). The UK Biobank holds a vast array of health-related data from 488,000 people and is also following the health of those people. It has also previously released genetic data from the same people but crucially those data only contain information about single nucleotide variants and not repeated sections like the one in PER3 that we are interested in. However, the UK Biobank has now released an updated database of genetic variants that does include repeated sections of DNA. So, the rationale for this project, which will last 3 years, is to investigate the PER3 repeat variant in a much larger group of people whose health status has been extensively characterised. This means that we will be able to determine in much more detail how this variant in a circadian clock gene affects short and long-term health. This particular PER3 variant is common in the UK population; around 10% of us have two copies of the rare variant and around 45% carry one copy. Therefore, a much greater understanding of how this PER3 variant contributes to health could have an important public health impact.