{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPER1 is a central component of the molecular circadian clock that drives 24‐hour oscillations in gene expression across diverse tissues. Its mRNA and protein levels oscillate in a cell‐autonomous manner, and its activity is finely tuned by post‐translational modifications—such as phosphorylation by casein kinase I and subsequent ubiquitin–proteasome–mediated degradation via β‐TRCP—and by regulated nuclear entry through import factors like KPNB1. Such molecular control mechanisms ensure that PER1 helps maintain proper timing of the transcription–translation feedback loop essential for circadian homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDeregulation of PER1 is frequently observed in a range of human malignancies—including breast, prostate, colorectal, gastric, and skin cancers—where its reduced expression (often through promoter methylation or accelerated degradation) disrupts cell cycle regulation, apoptosis, and metabolism. In many cancer models, diminished PER1 levels are linked to impaired DNA damage responses, diminished checkpoint function (via interaction with proteins like ATM and Chk2), and aberrant activation of oncogenic pathways such as PI3K/AKT, resulting in increased proliferation, metabolic reprogramming (for example, altered glycolytic flux), and therapy resistance. Restoration or overexpression of PER1 enhances apoptosis and suppresses tumor growth, underscoring its potential role as a tumor suppressor and a promising target for chronotherapeutic interventions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in cancer, PER1 genetic variants and altered expression patterns are implicated in neuropsychiatric and peripheral disorders. Associations of PER1 polymorphisms with bipolar disorder, autism spectrum disorder, attention‐deficit/hyperactivity disorder, and sleep and mood disturbances (including those observed in obstructive sleep apnoea) point to its wider influence on brain function and behavior. Furthermore, PER1 modulates glucocorticoid responsiveness and metabolic regulation in tissues such as leukocytes, bone marrow, retina, and kidney—functions that underscore its integrative role in synchronizing peripheral physiology with central circadian timing. These diverse observations highlight PER1 as an important nexus linking circadian regulation with systemic health and disease susceptibility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Koyomi Miyazaki, Takahiro Nagase, Miho Mesaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20031308"}], "href": "https://doi.org/10.1042/BJ20031308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14750904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14750904"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takahiro Shirogane, Jianping Jin, Xiaolu L Ang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502862200"}], "href": "https://doi.org/10.1074/jbc.M502862200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15917222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15917222"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jayshan D Carpen, Malcolm von Schantz, Marcel Smits, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A silent polymorphism in the PER1 gene associates with extreme diurnal preference in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10038-006-0060-y"}], "href": "https://doi.org/10.1007/s10038-006-0060-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17051316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17051316"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "B Nicholas, V Rudrasingham, S Nash, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4001953"}], "href": "https://doi.org/10.1038/sj.mp.4001953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17264841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17264841"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hiroyuki Fukuya, Noriaki Emoto, Hidemi Nonaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian expression of clock genes in human peripheral leukocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2007.01.063"}], "href": "https://doi.org/10.1016/j.bbrc.2007.01.063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17274950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17274950"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Oleg Tsinkalovsky, Rune Smaaland, Benedikte Rosenlund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian variations in clock gene expression of human bone marrow CD34+ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Rhythms (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0748730406299078"}], "href": "https://doi.org/10.1177/0748730406299078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17440215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17440215"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gianluca Tosini, Alec J Davidson, Chiaki Fukuhara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of a circadian clock in mammalian photoreceptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.07-8371com"}], "href": "https://doi.org/10.1096/fj.07-8371com"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17621597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17621597"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Shintaro Komoto, Hisataka Kondo, Osamu Fukuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparison of β-adrenergic and glucocorticoid signaling on clock gene and osteoblast-related gene expressions in human osteoblast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chronobiol Int (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/07420528.2011.636496"}], "href": "https://doi.org/10.3109/07420528.2011.636496"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22217103"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22217103"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yool Lee, A Reum Jang, Lauren J Francey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KPNB1 mediates PER/CRY nuclear translocation and circadian clock function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.08647"}], "href": "https://doi.org/10.7554/eLife.08647"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26319354"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26319354"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shou-Tung Chen, Kong-Bung Choo, Ming-Feng Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgi075"}], "href": "https://doi.org/10.1093/carcin/bgi075"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15790588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15790588"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sigal Gery, Naoki Komatsu, Lilit Baldjyan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2006.03.038"}], "href": "https://doi.org/10.1016/j.molcel.2006.03.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16678109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16678109"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sherry L Winter, Lucine Bosnoyan-Collins, Dushanthi Pinnaduwage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1593/neo.07595"}], "href": "https://doi.org/10.1593/neo.07595"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17971899"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17971899"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yueh-Min Lin, Julia H Chang, Kun-Tu Yeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disturbance of circadian gene expression in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Carcinog (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mc.20446"}], "href": "https://doi.org/10.1002/mc.20446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18444243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18444243"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Shou-Jen Kuo, Shou-Tung Chen, Kun-Tu Yeh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disturbance of circadian gene expression in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virchows Arch (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00428-009-0761-7"}], "href": "https://doi.org/10.1007/s00428-009-0761-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19296127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19296127"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Qi Cao, Sigal Gery, Azadeh Dashti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for the clock gene per1 in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-4199"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-4199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19752089"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19752089"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Yong Zhu, Richard G Stevens, Aaron E Hoffman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-09-0648"}], "href": "https://doi.org/10.1158/0008-5472.CAN-09-0648"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19934327"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19934327"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Hongji Dai, Lina Zhang, Mingli Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of polymorphisms in circadian pathway genes in breast tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res Treat (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10549-010-1231-2"}], "href": "https://doi.org/10.1007/s10549-010-1231-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20978934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20978934"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Takashi Oshima, Seiich Takenoshita, Makoto Akaike, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2011.1207"}], "href": "https://doi.org/10.3892/or.2011.1207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21380491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21380491"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Zsuzsanna Lengyel, Csenge Lovig, Siri Kommedal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-012-0611-0"}], "href": "https://doi.org/10.1007/s13277-012-0611-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23242607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23242607"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Olivier Pluquet, Nicolas Dejeans, Marion Bouchecareilh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Posttranscriptional regulation of PER1 underlies the oncogenic function of IREα."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-3989"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-3989"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23752693"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23752693"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Peter C St John, Tsuyoshi Hirota, Steve A Kay, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spatiotemporal separation of PER and CRY posttranslational regulation in the mammalian circadian clock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1323618111"}], "href": "https://doi.org/10.1073/pnas.1323618111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24449901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24449901"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Han Zhao, Zhao-Lei Zeng, Jing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic relevance of Period1 (Per1) and Period2 (Per2) expression in human gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Clin Exp Pathol (2014)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24551282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24551282"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Jonathan A Hardman, Desmond J Tobin, Iain S Haslam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The peripheral clock regulates human pigmentation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2014.442"}], "href": "https://doi.org/10.1038/jid.2014.442"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25310406"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25310406"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kristen Solocinski, Jacob Richards, Sean All, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00197.2014"}], "href": "https://doi.org/10.1152/ajprenal.00197.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26377793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26377793"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Xiaobao Gong, Hong Tang, Kai Yang "}, {"type": "b", "children": [{"type": "t", "text": "PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-03563-5"}], "href": "https://doi.org/10.1038/s41419-021-03563-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33723221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33723221"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jiao Wang, Qiong Huang, Xingbin Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disrupting Circadian Rhythm via the PER1-HK2 Axis Reverses Trastuzumab Resistance in Gastric Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-21-1820"}], "href": "https://doi.org/10.1158/0008-5472.CAN-21-1820"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35255118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35255118"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Caroline M Nievergelt, Daniel F Kripke, Thomas B Barrett, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30252"}], "href": "https://doi.org/10.1002/ajmg.b.30252"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16528748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16528748"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "L W Chu, Y Zhu, K Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variants in circadian genes and prostate cancer risk: a population-based study in China."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate Cancer Prostatic Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.pcan.4501024"}], "href": "https://doi.org/10.1038/sj.pcan.4501024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17984998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17984998"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Jiajun Shi, Jacqueline K Wittke-Thompson, Judith A Badner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30714"}], "href": "https://doi.org/10.1002/ajmg.b.30714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18228528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18228528"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "N Burioka, S Koyanagi, M Endo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clock gene dysfunction in patients with obstructive sleep apnoea syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Respir J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1183/09031936.00138207"}], "href": "https://doi.org/10.1183/09031936.00138207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18321934"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18321934"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Jessica Lasky-Su, Benjamin M Neale, Barbara Franke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet B Neuropsychiatr Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.b.30867"}], "href": "https://doi.org/10.1002/ajmg.b.30867"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18821565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18821565"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Virginia Soria, Erika Martínez-Amorós, Geòrgia Escaramís, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/npp.2009.230"}], "href": "https://doi.org/10.1038/npp.2009.230"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20072116"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20072116"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Timothy E Reddy, Jason Gertz, Gregory E Crawford, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00062-12"}], "href": "https://doi.org/10.1128/MCB.00062-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22801371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22801371"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Zhuqin Gu, BinBin Wang, Yong-Biao Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of ARNTL and PER1 genes with Parkinson's disease: a case-control study of Han Chinese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep15891"}], "href": "https://doi.org/10.1038/srep15891"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26507264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26507264"}]}]}]}