ArticleProceedings of the National Academy of Sciences of the United States of America2016
A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk.Nature genetics · 2026Pooled it
- Time matters: circadian genetics and the molecular logic of human health and disease.Nature reviews. Genetics · 2026Review
- Emerging genetics of sleep and circadian disorders.Current opinion in pediatrics · 2026Article
- Article
- Biochemical mechanism of the mammalian circadian clock.FEBS letters · 2026Review
- PER3 expression in granulosa cells of women with polycystic ovary syndrome: a potential role of the ovarian peripheral clock in infertility.Molecular biology reports · 2026Article
- Effects of seasonal factors on brain function: Systematic review and future perspectives.iScience · 2025Article
- Period3 modulates the NADJournal of advanced research · 2025Article
- Methods for Assessment of Sleep and Circadian Rhythms in Cardiovascular Research.Current hypertension reports · 2025Review
- Multi-SNP Haplotypes in CircadianGenes · 2025Article
- Rare variants inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Human PERIOD3 variants lead to winter depression-like behaviours via glucocorticoid signalling.Nature metabolism · 2024Article
- Sleep and circadian disruption in bipolar disorders: From psychopathology to digital phenotyping in clinical practice.Psychiatry and clinical neurosciences · 2024Review
- Functional and regulatory diversification of Period genes responsible for circadian rhythm in vertebrates.G3 (Bethesda, Md.) · 2024Article
- Moderating effects of PER3 gene DNA methylation on the association between problematic mobile phone use and chronotype among Chinese young adults: Focus on gender differences.Journal of behavioral addictions · 2024Article
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- Circadian neurogenetics and its implications in neurophysiology, behavior, and chronomedicine.Neuroscience and biobehavioral reviews · 2024Review
- Clock geneActa biochimica et biophysica Sinica · 2023Article
- Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
In humans, the connection between sleep and mood has long been recognized, although direct molecular evidence is lacking. We identified two rare variants in the circadian clock gene PERIOD3 (PER3-P415A/H417R) in humans with familial advanced sleep phase accompanied by higher Beck Depression Inventory and seasonality scores. hPER3-P415A/H417R transgenic mice showed an altered circadian period under constant light and exhibited phase shifts of the sleep-wake cycle in a short light period (photoperiod) paradigm. Molecular characterization revealed that the rare variants destabilized PER3 and failed to stabilize PERIOD1/2 proteins, which play critical roles in circadian timing. Although hPER3-P415A/H417R-Tg mice showed a mild depression-like phenotype, Per3 knockout mice demonstrated consistent depression-like behavior, particularly when studied under a short photoperiod, supporting a possible role for PER3 in mood regulation. These findings suggest that PER3 may be a nexus for sleep and mood regulation while fine-tuning these processes to adapt to seasonal changes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.