Familial Advanced Sleep Phase (FASPS): An Inherited Body Clock Set Hours Early
Familial advanced sleep phase (FASPS) is an inherited tendency to fall asleep and wake hours early, linked to PER2, CK1-delta and CRY2 variants in studied families.
In this article5 sections
Melatonin onset in an average adult, per the reference sample the 2016 eLife study compared against, arrives around 8:50 PM. In one woman from the studied family it began at 4:41 PM, 3.35 standard deviations earlier and within the earliest 0.05% of the reference group. She, her fraternal twin sister and their mother all slept and woke far earlier than the people around them. The pattern is called familial advanced sleep phase, usually shortened to FASPS.
Definition
FASPS is an inherited tendency for the body clock to sit several hours ahead of the local day, so sleepiness arrives in the early evening and waking comes in the small hours. In studied families it tracks variants in clock genes. The CRY2 A260T variant is rare (allele frequency 0.00008 in the ExAC database), but Hirano and colleagues estimate FASP itself at about 0.5% of the general population, from unpublished data.
Three genes, three families
| Gene | Variant | Source |
|---|---|---|
| PER2 | S662G (serine to glycine at position 662) | Toh et al., Science, 2001 |
| CSNK1D (CK1-delta) | T44A (threonine to alanine at position 44), which lowered the enzyme’s activity | Xu et al., Nature, 2005 |
| CRY2 | A260T (alanine to threonine at position 260) | Hirano et al., eLife, 2016 |
Jones and colleagues described the first FASPS family in Nature Medicine in 1999. The Toh paper placed the PER2 change in a region thought to be a phosphorylation site for casein kinase 1, and Xu and colleagues (2005) found the CK1-delta variant in a separate family.
The numbers in the CRY2 family
Beyond the 4:41 PM melatonin onset, the two affected twins scored 84 and 72 on the Horne-Ostberg morningness questionnaire. The A260T change makes the CRY2 protein bind more tightly to FBXL3, a ligase that marks proteins for destruction, so CRY2 is degraded faster.
Why faster protein turnover moves the clock
The circadian oscillator is a feedback loop, and its period depends on how long its repressor proteins last. Shorten their lifetime and the loop completes a cycle sooner. Picture a pendulum that is slightly short: each swing is quicker, and the error accumulates until the clock runs ahead of the room. In mice carrying the human CRY2 variant the free-running period shortened by about 0.2 hours. Light and social cues pull a human clock back toward 24 hours each day, and the result in these families is a phase set hours early. The paper does not explain how a 0.2-hour mouse shift relates to a multi-hour human advance.
Where it sits among other early-morning patterns
FASPS is a family trait that tracks a gene variant, not a lifestyle outcome. It differs from natural short sleepers, who need less sleep rather than different timing; two authors of the CRY2 paper, Ying-Hui Fu and Louis Ptáček, also work on the DEC2 and related short-sleep variants. Its mirror image, delayed sleep phase, shows up mostly in adolescence.