Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans

Chang, Anne Marie; Duffy, Jeanne F.; Buxton, Orfeu M.; Lane, Jacqueline M.; Aeschbach, Daniel; Anderson, Clare; Bjonnes, Andrew; Cain, Sean W.; Cohen, Daniel; Frayling, Timothy M.; Gooley, Joshua J.; Jones, Samuel E.; Klerman, Elizabeth B.; Lockley, Steven W.; Münch, Mirjam; Rajaratnam, Shanthakumar M W; Rueger, Melanie; Rutter, Martin K.; Santhi, Nayantara; Scheuermaier, Karine; Reen, Eliza Van; Weedon, Michael N.; Czeisler, Charles A.; Scheer, Frank A.J.L.; Saxena, Richa

doi:10.1038/s41598-019-41712-1

Cited by 28 publications

(14 citation statements)

References 54 publications

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“…Human Per2 is present on chromosome number 2 [14], to be precise on 2q37.3 [15]. Per2 is one of the circadian pacemaker [15] that plays an important role in circadian time keeping in humans [27]. Per2 is a positive regulator of circadian gene expression [11,16,21] but possibly delays the clock [11,23].…”

Section: Per2 Genementioning

confidence: 99%

Analysis of simple sequence repeats in Period genes in mammals

Gunja¹

2021

J App Biol Biotech

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Circadian rhythm is driven by the circadian clock. One of the core clock genes identified is Period (Per) in Drosophila and Period1 (Per1), Period2 (Per2), and Period3 (Per3) in mammals. The present study examines the presence of perfect simple sequence repeats (SSRs) in human Period genes and their orthologues in chimpanzee, gorilla, orangutan, gibbon, and mouse. Comparisons of all Per genes show a higher density of SSRs in Per1 of all organisms followed by Per3 and Per2 with exceptions. Possibly due to higher chances of mutations, CG-rich repeats are not abundant in Per genes. This analysis shows gene and species-specific distribution of repeats along with region-specific distribution of repeat types and repeat motifs in exons and introns of the Per genes. There is diverse distribution of CG-rich repeat types and motifs in the three Per and also in exons and introns of the three genes in different organisms. Long perfect SSRs are generally not common. Since perfect SSRs are prone to mutations, there is a need to study SSRs, especially found in exons of human Per genes which could serve as markers for investigators to study the role of such SSRs in Per-related disorders.

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Section: Per2 Genementioning

confidence: 99%

Analysis of simple sequence repeats in Period genes in mammals

Gunja¹

2021

J App Biol Biotech

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“…A length polymorphism in the PER3 gene due to a variable-number tandem repeat (4 or 5 repeats) has been linked to DSP in which the longer allele is associated with morningness and the shorter allele with eveningness [50]. A missense PER2 variant, Rs35333999, is associated with longer circadian period and later chronotype [40,51]. A single mutation in the CRY1 gene, CRY1 c.1657 + 3 A > C, has been identified that confers an autosomal dominant DSP trait [52].…”

Section: Gwas Of Chronotypementioning

confidence: 99%

Genetics of the human circadian clock and sleep homeostat

Ashbrook

Krystal

et al. 2019

Neuropsychopharmacol.

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Timing and duration of sleep are controlled by the circadian system, which keeps an~24-h internal rhythm that entrains to environmental stimuli, and the sleep homeostat, which rises as a function of time awake. There is a normal distribution across the population in how the circadian system aligns with typical day and night resulting in varying circadian preferences called chronotypes. A portion of the variation in the population is controlled by genetics as shown by the single-gene mutations that confer extreme early or late chronotypes. Similarly, there is a normal distribution across the population in sleep duration. Genetic variations have been identified that lead to a short sleep phenotype in which individuals sleep only 4-6.5 h nightly. Negative health consequences have been identified when individuals do not sleep at their ideal circadian timing or are sleep deprived relative to intrinsic sleep need. Whether familial natural short sleepers are at risk of the health consequences associated with a short sleep duration based on population data is not known. More work needs to be done to better assess for an individual's chronotype and degree of sleep deprivation to answer these questions.

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“…It is a key clock gene that regulates circadian rhythms of mammals on the level of pathology, physiology and gene expression. 7 Interruption in the expression of PER2 can lead to reduction in the transcription level of other clock genes. 8 In addition, a previous study which has also shown an interaction between PER2 and inflammation cytokine, shows the expression of PER2 reduced in synchronized fibroblasts after TNF-a treatment.…”

Section: Introductionmentioning

confidence: 99%

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus

Dan

Zhao

Mao

et al. 2021

Lupus

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The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between Period 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls ( p = 0.030, p = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.

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Chronotype Genetic Variant in PER2 is Associated with Intrinsic Circadian Period in Humans

Cited by 28 publications

References 54 publications

Analysis of simple sequence repeats in Period genes in mammals

Analysis of simple sequence repeats in Period genes in mammals

Genetics of the human circadian clock and sleep homeostat

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus

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