A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
Autoři:
Orna Levran aff001; Matthew Randesi aff001; John Rotrosen aff002; Jurg Ott aff003; Miriam Adelson aff004; Mary Jeanne Kreek aff001
Působiště autorů:
The Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York, United States of America
aff001; NYU School of Medicine, New York, New York, United States of America
aff002; The Laboratory of Statistical Genetics, The Rockefeller University, New York, New York, United States of America
aff003; Dr. Miriam and Sheldon G. Adelson Clinic for Drug Abuse Treatment and Research, Las Vegas, Nevada, United States of America
aff004
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0224399
Souhrn
There is a reciprocal relationship between the circadian and the reward systems. Polymorphisms in several circadian rhythm-related (clock) genes were associated with drug addiction. This study aims to search for associations between 895 variants in 39 circadian rhythm-related genes and opioid addiction (OUD). Genotyping was performed with the Smokescreen® array. Ancestry was verified by principal/MDS component analysis and the sample was limited to European Americans (EA) (OUD; n = 435, controls; n = 138). Nominally significant associations (p < 0.01) were detected for several variants in genes encoding vasoactive intestinal peptide receptor 2 (VIPR2), period circadian regulator 2 (PER2), casein kinase 1 epsilon (CSNK1E), and activator of transcription and developmental regulator (AUTS2), but no signal survived correction for multiple testing. There was intriguing association signal for the untranslated region (3’ UTR) variant rs885863 in VIPR2, (p = .0065; OR = 0.51; 95% CI 0.31–0.51). The result was corroborated in an independent EA OUD sample (n = 398, p = 0.0036; for the combined samples). Notably, this SNP is an expression quantitative trait locus (cis-eQTL) for VIPR2 and a long intergenic non-coding RNA, lincRNA 689, in a tissue-specific manner, based on the Genotype-Tissue Expression (GTEx) project. Vasoactive intestinal peptide (VIP) is an important peptide of light-activated suprachiasmatic nucleus cells. It regulates diverse physiological processes including circadian rhythms, learning and memory, and stress response. This is the first report of an association of a VIPR2 variant and OUD. Additionally, analysis of combinations of single nucleotide polymorphisms (SNPs) genotypes revealed an association of PER2 SNP rs80136044, and SNP rs4128839, located 41.6 kb downstream of neuropeptide Y receptor type 1 gene, NPY1R (p = 3.4 × 10−6, OR = 11.4, 95% CI 2.7–48.2). The study provides preliminary insight into the relationship between genetic variants in circadian rhythm genes and long non-coding RNA (lncRNAs) in their vicinity, and opioid addiction.
Klíčová slova:
Gene regulation – Molecular genetics – Addiction – Opioids – Circadian rhythms – Long non-coding RNAs – Regulator genes – Circadian oscillators
Zdroje
1. Gulick D, Gamsby JJ. Racing the clock: The role of circadian rhythmicity in addiction across the lifespan. Pharmacol Ther. 2018;188:124–39. doi: 10.1016/j.pharmthera.2018.03.003 29551440
2. Kreek MJ, Levran O, Reed B, Schlussman SD, Zhou Y, Butelman ER. Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. J Clin Invest. 2012;122(10):3387–93. doi: 10.1172/JCI60390 23023708
3. Logan RW, Williams WP 3rd, McClung CA. Circadian rhythms and addiction: mechanistic insights and future directions. Behav Neurosci. 2014;128(3):387–412. doi: 10.1037/a0036268 24731209
4. Perreau-Lenz S, Spanagel R. The effects of drugs of abuse on clock genes. Drug News Perspect. 2008;21(4):211–7. doi: 10.1358/dnp.2008.21.4.1213350 18560620
5. Falcon E, McClung CA. A role for the circadian genes in drug addiction. Neuropharmacology. 2009;56 Suppl 1:91–6.
6. Perreau-Lenz S, Spanagel R. Clock genes x stress x reward interactions in alcohol and substance use disorders. Alcohol. 2015;49(4):351–7. doi: 10.1016/j.alcohol.2015.04.003 25943583
7. Kovanen L, Saarikoski ST, Haukka J, Pirkola S, Aromaa A, Lonnqvist J, et al. Circadian clock gene polymorphisms in alcohol use disorders and alcohol consumption. Alcohol Alcohol. 2010;45(4):303–11. doi: 10.1093/alcalc/agq035 20554694
8. Young MW, Kay SA. Time zones: a comparative genetics of circadian clocks. Nat Rev Genet. 2001;2(9):702–15. doi: 10.1038/35088576 11533719
9. Reischl S, Kramer A. Kinases and phosphatases in the mammalian circadian clock. FEBS Lett. 2011;585(10):1393–9. doi: 10.1016/j.febslet.2011.02.038 21376720
10. Tamaru T, Takamatsu K. Circadian modification network of a core clock driver BMAL1 to harmonize physiology from brain to peripheral tissues. Neurochem Int. 2018;119:11–6. doi: 10.1016/j.neuint.2017.12.013 29305918
11. Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, et al. Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature. 2002;419(6909):841–4. doi: 10.1038/nature01123 12397359
12. Hughes AT, Piggins HD. Behavioral responses of Vipr2-/- mice to light. J Biol Rhythms. 2008;23(3):211–9. doi: 10.1177/0748730408316290 18487413
13. Mazuski C, Abel JH, Chen SP, Hermanstyne TO, Jones JR, Simon T, et al. Entrainment of Circadian Rhythms Depends on Firing Rates and Neuropeptide Release of VIP SCN Neurons. Neuron. 2018;99(3):555–63.e5. doi: 10.1016/j.neuron.2018.06.029 30017392
14. Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466–75. doi: 10.1038/nrendo.2014.78 24863387
15. Cleck JN, Blendy JA. Making a bad thing worse: adverse effects of stress on drug addiction. J Clin Invest. 2008;118(2):454–61. doi: 10.1172/JCI33946 18246196
16. Levran O, Peles E, Randesi M, Correa da Rosa J, Ott J, Rotrosen J, et al. Dopaminergic pathway polymorphisms and heroin addiction: further support for association of CSNK1E variants. Pharmacogenomics. 2014;15(16):2001–9. doi: 10.2217/pgs.14.145 25521358
17. Levran O, Londono D, O’Hara K, Nielsen DA, Peles E, Rotrosen J, et al. Genetic susceptibility to heroin addiction: a candidate gene association study. Genes Brain Behav. 2008;7(7):720–9. doi: 10.1111/j.1601-183X.2008.00410.x 18518925
18. Levran O, Peles E, Randesi M, Li Y, Rotrosen J, Ott J, et al. Stress-related genes and heroin addiction: a role for a functional FKBP5 haplotype. Psychoneuroendocrinology. 2014;45:67–76. doi: 10.1016/j.psyneuen.2014.03.017 24845178
19. Levran O, Correa da Rosa J, Randesi M, Rotrosen J, Adelson M, Kreek MJ. A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction. PLoS One. 2018;13(6):e0199951. doi: 10.1371/journal.pone.0199951 29953524
20. McLellan AT, Kushner H, Metzger D, Peters R, Smith I, Grissom G, et al. The Fifth Edition of the Addiction Severity Index. J Subst Abuse Treat. 1992;9(3):199–213. doi: 10.1016/0740-5472(92)90062-s 1334156
21. Kellogg SH, McHugh PF, Bell K, Schluger JH, Schluger RP, LaForge KS, et al. The Kreek-McHugh-Schluger-Kellogg scale: a new, rapid method for quantifying substance abuse and its possible applications. Drug Alcohol Depend. 2003;69(2):137–50. doi: 10.1016/s0376-8716(02)00308-3 12609695
22. Lee JD, Nunes EV Jr, Novo P, Bachrach K, Bailey GL, Bhatt S, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2017.
23. Baurley JW, Edlund CK, Pardamean CI, Conti DV, Bergen AW. Smokescreen: a targeted genotyping array for addiction research. BMC Genomics. 2016;17:145. doi: 10.1186/s12864-016-2495-7 26921259
24. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome. Science. 2002;296(5576):2225–9. doi: 10.1126/science.1069424 12029063
25. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75. doi: 10.1086/519795 17701901
26. Hoh J, Wille A, Ott J. Trimming, weighting, and grouping SNPs in human case-control association studies. Genome Res. 2001;11(12):2115–9. doi: 10.1101/gr.204001 11731502
27. Wang G, Yang Y, Ott J. Genome-wide conditional search for epistatic disease-predisposing variants in human association studies. Hum Hered. 2010;70(1):34–41. doi: 10.1159/000293722 20413980
28. Zhang Q, Wang S, Ott J. Combining identity by descent and association in genetic case-control studies. BMC Genet. 2008;9(1):42.
29. Soria V, Martinez-Amoros E, Escaramis G, Valero J, Perez-Egea R, Garcia C, et al. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology. 2010;35(6):1279–89. doi: 10.1038/npp.2009.230 20072116
30. Harmar AJ, Fahrenkrug J, Gozes I, Laburthe M, May V, Pisegna JR, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166(1):4–17. doi: 10.1111/j.1476-5381.2012.01871.x 22289055
31. Ago Y, Hayata-Takano A, Kawanai T, Yamauchi R, Takeuchi S, Cushman JD, et al. Impaired extinction of cued fear memory and abnormal dendritic morphology in the prelimbic and infralimbic cortices in VPAC2 receptor (VIPR2)-deficient mice. Neurobiol Learn Mem. 2017;145:222–31. doi: 10.1016/j.nlm.2017.10.010 29030297
32. Vacic V, McCarthy S, Malhotra D, Murray F, Chou HH, Peoples A, et al. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia. Nature. 2011;471(7339):499–503. doi: 10.1038/nature09884 21346763
33. Wu Y, Wang W, Jiang W, Yao J, Zhang D. An investigation of obesity susceptibility genes in Northern Han Chinese by targeted resequencing. Medicine (Baltimore). 2017;96(7):e6117.
34. Parikshak NN, Swarup V, Belgard TG, Irimia M, Ramaswami G, Gandal MJ, et al. Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism. Nature. 2016;540(7633):423–7. doi: 10.1038/nature20612 27919067
35. Liu X, Zhu Q, Guo Y, Xiao Z, Hu L, Xu Q. LncRNA LINC00689 promotes the growth, metastasis and glycolysis of glioma cells by targeting miR-338-3p/PKM2 axis. Biomed Pharmacother. 2019;117:109069. doi: 10.1016/j.biopha.2019.109069 31181442
36. Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, et al. Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem. 2003;278(42):41519–27. doi: 10.1074/jbc.M304564200 12865428
37. Zhou P, Ross RA, Pywell CM, Liangpunsakul S, Duffield GE. Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis. Sci Rep. 2014;4:3725. doi: 10.1038/srep03725 24430730
38. Dang W, Zhang Q, Zhu YS, Lu XY. The evidence for the contribution of the autism susceptibility candidate 2 (AUTS2) gene in heroin dependence susceptibility. J Mol Neurosci. 2014;54(4):811–9. doi: 10.1007/s12031-014-0421-5 25398668
39. Chen YH, Liao DL, Lai CH, Chen CH. Genetic analysis of AUTS2 as a susceptibility gene of heroin dependence. Drug Alcohol Depend. 2013;128(3):238–42. doi: 10.1016/j.drugalcdep.2012.08.029 22995765
40. Schumann G, Coin LJ, Lourdusamy A, Charoen P, Berger KH, Stacey D, et al. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc Natl Acad Sci U S A. 2011;108(17):7119–24. doi: 10.1073/pnas.1017288108 21471458
41. Savage JE, Jansen PR, Stringer S, Watanabe K, Bryois J, de Leeuw CA, et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat Genet. 2018;50(7):912–9. doi: 10.1038/s41588-018-0152-6 29942086
42. Oksenberg N, Ahituv N. The role of AUTS2 in neurodevelopment and human evolution. Trends Genet. 2013;29(10):600–8. doi: 10.1016/j.tig.2013.08.001 24008202
43. Engmann O, Labonte B, Mitchell A, Bashtrykov P, Calipari ES, Rosenbluh C, et al. Cocaine-Induced Chromatin Modifications Associate With Increased Expression and Three-Dimensional Looping of Auts2. Biol Psychiatry. 2017.
44. Wang Y, Zhu Y, Wang W, Wu F, Cui H, Xun X, et al. A population-based association study of casein kinase 1 epsilon loci with heroin dependence in Han Chinese. J Mol Neurosci. 2014;53(2):143–9. doi: 10.1007/s12031-013-0186-2 24338102
45. Cheong JK, Virshup DM. Casein kinase 1: Complexity in the family. Int J Biochem Cell Biol. 2011;43(4):465–9. doi: 10.1016/j.biocel.2010.12.004 21145983
46. Hosseini E, Bagheri-Hosseinabadi Z, De Toma I, Jafarisani M, Sadeghi I. The importance of long non-coding RNAs in neuropsychiatric disorders. Mol Aspects Med. 2019.
47. Ransohoff JD, Wei Y, Khavari PA. The functions and unique features of long intergenic non-coding RNA. Nat Rev Mol Cell Biol. 2018;19(3):143–57. doi: 10.1038/nrm.2017.104 29138516
48. Walker DM, Nestler EJ. Neuroepigenetics and addiction. Handb Clin Neurol. 2018;148:747–65. doi: 10.1016/B978-0-444-64076-5.00048-X 29478612
49. Michelhaugh SK, Lipovich L, Blythe J, Jia H, Kapatos G, Bannon MJ. Mining Affymetrix microarray data for long non-coding RNAs: altered expression in the nucleus accumbens of heroin abusers. J Neurochem. 2011;116(3):459–66. doi: 10.1111/j.1471-4159.2010.07126.x 21128942
50. Albertson DN, Schmidt CJ, Kapatos G, Bannon MJ. Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006;31(10):2304–12. doi: 10.1038/sj.npp.1301089 16710320
51. Guo X, Lin W, Bao J, Cai Q, Pan X, Bai M, et al. A Comprehensive cis-eQTL Analysis Revealed Target Genes in Breast Cancer Susceptibility Loci Identified in Genome-wide Association Studies. Am J Hum Genet. 2018;102(5):890–903. doi: 10.1016/j.ajhg.2018.03.016 29727689
Článok vyšiel v časopise
PLOS One
2019 Číslo 11
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Ne každé mimoděložní těhotenství musí končit salpingektomií
- Masturbační chování žen v ČR − dotazníková studie
- Těžké menstruační krvácení může značit poruchu krevní srážlivosti. Jaký management vyšetření a léčby je v takovém případě vhodný?
Najčítanejšie v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF
- Pathways to conspiracy: The social and linguistic precursors of involvement in Reddit’s conspiracy theory forum
- Urticating setae of tarantulas (Araneae: Theraphosidae): Morphology, revision of typology and terminology and implications for taxonomy
Zvýšte si kvalifikáciu online z pohodlia domova
Všetky kurzy