精神分裂症相关单核苷酸多态性调控microRNA功能研究进展

doi:10.16288/j.yczz.19-126

遗传 ›› 2019, Vol. 41 ›› Issue (8): 677-685.doi: 10.16288/j.yczz.19-126

精神分裂症相关单核苷酸多态性调控microRNA功能研究进展

梁文权¹,侯豫²,赵存友¹()

^1. 南方医科大学基础医学院医学遗传学教研室,广州 510515
^2. 陆军总医院附属八一儿童医院神经发育科,北京 100700

收稿日期:2019-05-08 修回日期:2019-07-07 出版日期:2019-08-20 发布日期:2019-08-05
通讯作者: 赵存友 E-mail:cyzhao@smu.edu.cn
作者简介:梁文权,硕士在读研究生,专业方向：表观遗传。E-mail:wen1390229749@163.com
基金资助:
广东省科技计划项目(2019B030316032);广州市科技计划项目(201804010259);国家自然科学基金项目资助(81601175);国家自然科学基金项目资助(81671333)

Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function

Liang Wenquan¹,Hou Yu²,Zhao Cunyou¹()

^1. Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
^2. Department of Pediatric Neurology, Affiliated BaYi Children's Hospital, PLA Army General Hospital, Beijing 100700, China

Received:2019-05-08 Revised:2019-07-07 Online:2019-08-20 Published:2019-08-05
Contact: Zhao Cunyou E-mail:cyzhao@smu.edu.cn
Supported by:
Supported by the Guangdong Science and Technology Foundation(2019B030316032);The Guangzhou Science and Technology Foundatio(201804010259);The National Natural Science Foundation of China(81601175);The National Natural Science Foundation of China(81671333)

摘要/Abstract

摘要：

MicroRNA (miRNAs)是一类长约22nt且对基因表达具有广泛的调控作用的非编码RNA,并在神经元增殖、分化和发育成熟的过程中扮演重要角色。近年来全基因组关联研究(genome-wide association studies, GWAS)发现了众多的精神分裂症相关单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点多位于非编码区,表明miRNA在精神分裂症的发病过程中存在重要作用。本文综述了精神分裂症相关SNP与miRNA可能发生相互作用的4种机制(SNP位于miRNA基因、SNP位于miRNA宿主基因、SNP位于miRNA种子序列和SNP位于miRNA结合位点),为研究miRNA在精神分裂症发生发展中的作用提供参考。

关键词: 全基因组关联研究, 单核苷酸多态性, 微小RNA, 精神分裂症

Abstract:

MicroRNAs (miRNAs) compose a class of non-coding transcripts with a mean length of 22 nucleotides, and play critical roles in regulating gene expression in the process of development, proliferation and differentiation of neurons. Recent genome-wide association studies (GWAS) find most of schizophrenia-associated single nucleotide polymorphisms (SNPs) locating in the non-coding regions, providing functional implications of miRNAs in the development of schizophrenia. In this review, we highlight the interplays between GWAS-SNPs and miRNAs in four perspectives: SNP in miRNA gene; miRNA located in the host gene; SNP located in the miRNA’s seed sequence; SNP located in the miRNA’s binding site. We also speculate on the future research on the role of miRNA in the development of schizophrenia.

Key words: GWAS, SNP, miRNA, schizophrenia

梁文权,侯豫,赵存友. 精神分裂症相关单核苷酸多态性调控microRNA功能研究进展[J]. 遗传, 2019, 41(8): 677-685.

Liang Wenquan,Hou Yu,Zhao Cunyou. Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function[J]. Hereditas(Beijing), 2019, 41(8): 677-685.

参考文献

[1]	Plomin R, Owen MJ, Mcguffin P . The genetic basis of complex human behaviors. Science, 1994,264(5166):1733-1739.
[2]	O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT . C-Myc-regulated microRNAs modulate E2F1 expression. Nature, 2005,435(7043):839-843.
[3]	Stark A, Brennecke J, Bushati N, Russell RB, Cohen SM . Animal MicroRNAs confer robustness to gene expression and have a significant impact on 3'UTR evolution. Cell, 2005,123(6):1133-1146.
[4]	Gong Y, Wu CN, Xu J, Feng G, Xing QH, Fu W, Li C, He L, Zhao XZ . Polymorphisms in microRNA target sites influence susceptibility to schizophrenia by altering the binding of miRNAs to their targets. Eur Neuropsychopharm, 2013,23(10):1182-1189.
[5]	Friedman RC, Farh KK, Burge CB, Bartel DP . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res, 2009,19(1):92-105.
[6]	Sullivan PF, Lin D, Tzeng JY, van den Oord E, Perkins D, Stroup TS, Wagner M, Lee S, Wright FA, Zou F, Liu W, Downing AM, Lieberman J, Close SL . Genomewide association for schizophrenia in the CATIE study: results of stage 1. Mol Psychiatry, 2008,13(6):570-584.
[7]	Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia- associated genetic loci. Nature, 2014,511(7510):421-427.
[8]	Li Z, Chen J, Yu H, He L, Xu Y, Zhang D, Yi Q, Li C, Li X, Shen J, Song Z, Ji W, Wang M, Zhou J, Chen B, Liu Y, Wang J, Wang P, Yang P, Wang Q, Feng G, Liu B, Sun W, Li B, He G, Li W, Wan C, Xu Q, Li W, Wen Z, Liu K, Huang F, Ji J, Ripke S, Yue W, Sullivan PF, O'Donovan MC, Shi Y . Genome-wide association analysis identifies 30 new susceptibility loci for schizophrenia. Nat Genet, 2017,49(11):1576-1583.
[9]	Pardiñas AF, Holmans P, Pocklington AJ, Escott-Price V, Ripke S, Carrera N, Legge SE, Bishop S, Cameron D, Hamshere ML, Han J, Hubbard L, Lynham A, Mantripragada K, Rees E, MacCabe JH, McCarroll SA, Baune BT, Breen G, Byrne EM, Dannlowski U, Eley TC, Hayward C, Martin NG, McIntosh AM, Plomin R, Porteous DJ, Wray NR, Caballero A, Geschwind DH, Huckins LM, Ruderfer DM, Santiago E, Sklar P, Stahl EA, Won H, Agerbo E, Als TD, Andreassen OA, B?kvad-Hansen M, Mortensen PB, Pedersen CB, B?rglum AD, Bybjerg-Grauholm J, Djurovic S, Durmishi N, Pedersen MG, Golimbet V, Grove J, Hougaard DM, Mattheisen M, Molden E, Mors O, Nordentoft M, Pejovic-Milovancevic M, Sigurdsson E, Silagadze T, Hansen CS, Stefansson K, Stefansson H, Steinberg S, Tosato S, Werge T,; GERAD Consortium; CRESTAR Consortium, Collier DA, Rujescu D, Kirov G, Owen MJ, O'Donovan MC, Walters JTR . Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nat Genet, 2018,50(3):381-389.
[10]	International Schizophrenia Consortium, Purcell SM, Wray N R, Stone JL, Visscher PM, O'Donovan MC, Sullivan PF, Sklar P . Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 2009,460(7256):748-752.
[11]	Schizophrenia Psychiatric Genome-Wide Association Study (GWAS)Consortium. Genome-wide association study identifies five new schizophrenia loci. Nat Genet, 2011,43(10):969-976.
[12]	Zhang P, Bian Y, Liu N, Tang Y, Pan C, Hu Y, Tang Z . The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: a meta-analysis. Compr Psychiatry, 2016,67:26-32.
[13]	Potkin SG, Macciardi F, Guffanti G, Fallon JH, Wang Q, Turner JA, Lakatos A, Miles MF, Lander A, Vawter MP, Xie X . Identifying gene regulatory networks in schizophrenia. Neuroimage, 2010,53(3):839-847.
[14]	Green MJ, Cairns MJ, Wu J, Dragovic M, Jablensky A, Tooney PA, Scott RJ, Carr VJ . Australian Schizophrenia Research Bank. Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia. Mol Psychiatry, 2013,18(7):774-780.
[15]	Ning QL, Ma XD, Jiao LZ, Niu XR, Li JP, Wang B, Zhang H, Ma J . A family-base association study of the EGR3 gene polymorphisims and schizophrenia. Hereditas (Beijing), 2012,34(3):307-314.
[15]	宁启兰, 马旭东, 焦李子, 牛晓蓉, 李建鹏, 王彬, 张欢, 马捷 . 基于核心家系的EGR3基因与精神分裂症的关联研究. 遗传, 2012,34(3):307-314.
[16]	Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, Parker JS, Jin J, Hammond SM . MicroRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol, 2007,8(2):R27.
[17]	Murphy KC, Jones LA, Owen MJ . High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry, 1999,56(10):940-945.
[18]	Sellier C, Hwang VJ, Dandekar R, Durbin-Johnson B, Charlet-Berguerand N, Ander BP, Sharp FR, Angkustsiri K, Simon TJ, Tassone F . Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome. PLoS One, 2014,9(8):e103884.
[19]	Cattane N, Mora C, Lopizzo N, Lopizzo N, Borsini A, Maj C, Pedrini L, Rossi R, Riva MA, Pariante CM, Cattaneo A . Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR- 125b-1-3p in neurodevelopmental processes. Schizophr Res, 2019,205:63-75.
[20]	He K, Guo C, Guo M, Tong S, Zhang Q, Sun H, He L, Shi Y . Identification of serum microRNAs as diagnostic biomarkers for schizophrenia. Hereditas, 2019,156:23.
[21]	Guella I, Sequeira A, Rollins B, Morgan L, Torri F, van Erp TG, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Bunney WE, Potkin SG, Macciardi F, Vawter MP . Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. J Psychiatr Res, 2013,47(9):1215-1221.
[22]	Siegert S, Seo J, Kwon EJ, Rudenko A, Cho S, Wang W, Flood Z, Martorell AJ, Ericsson M, Mungenast AE, Tsai LH . The schizophrenia risk gene product miR-137 alters presynaptic plasticity. Nat Neurosci, 2015,18(7):1008-1016.
[23]	Hauberg ME, Holm-Nielsen MH, Mattheisen M, Askou AL, Grove J, Børglum AD, Corydon TJ . Schizophrenia risk variants affecting microRNA function and site-specific regulation of NT5C2 by miR-206. Eur Neuropsychopharm, 2016,26(9):1522-1526.
[24]	Parts L, Hedman Å K, Keildson S, Knights AJ, Abreu- Goodger C, van de Bunt M, Guerra-Assunção JA, Bartonicek N, van Dongen S, Mägi R, Nisbet J, Barrett A, Rantalainen M, Nica AC, Quail MA, Small KS, Glass D, Enright AJ, Winn J; MuTHER Consortium, Deloukas P, Dermitzakis ET, McCarthy MI, Spector TD, Durbin R, Lindgren CM . Extent, causes, and consequences of small RNA expression variation in human adipose tissue. PLoS Genet, 2012,8(5):e1002704.
[25]	Siddle KJ, Deschamps M, Tailleux L, Nédélec Y, Pothlichet J, Lugo-Villarino G, Libri V, Gicquel B, Neyrolles O, Laval G, Patin E, Barreiro LB, Quintana-Murci L . A genomic portrait of the genetic architecture and regulatory impact of microRNA expression in response to infection. Genome Res, 2014,24(5):850-859.
[26]	Huan T, Rong J, Liu C, Zhang X, Tanriverdi K, Joehanes R, Chen BH, Murabito JM, Yao C, Courchesne P, Munson PJ, O'Donnell CJ, Cox N, Johnson AD, Larson MG, Levy D, Freedman JE . Genome-wide identification of microRNA expression quantitative trait loci. Nat Commun, 2015,6:6601.
[27]	Winter J, Jung S, Keller S, Gregory RI, Diederichs S . Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol, 2009,11(3):228-234.
[28]	Baskerville S, Bartel DP . Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 2005,11(3):241-247.
[29]	Ruby JG, Jan CH, Bartel DP . Intronic microRNA precursors that bypass Drosha processing. Nature, 2007,448(7149):83-86.
[30]	Barik S . An intronic microRNA silences genes that are functionally antagonistic to its host gene. Nucleic Acids Res, 2008,36(16):5232-5241.
[31]	Kos A, Olde LoohuisNF, Wieczorek ML, Glennon JC, Martens GJ, Kolk SM, Aschrafi A . A potential regulatory role for intronic microRNA-338-3p for its host gene encoding apoptosis-associated tyrosine kinase. PLoS One, 2012,7(2):e31022.
[32]	Chun S, Du F, Westmoreland JJ, Han SB, Wang YD, Eddins D, Bayazitov IT, Devaraju P, Yu J, Mellado Lagarde MM, Anderson K, Zakharenko SS . Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in models of 22q11.2 microdeletion. Nat Med, 2017,23(1):39-48.
[33]	Kos A, de Mooij-Malsen AJ, van Bokhoven H, van Bokhoven H, Kaplan BB, Martens GJ, Kolk SM, Aschrafi A . MicroRNA-338 modulates cortical neuronal placement and polarity. RNA Biol, 2017,14(7):905-913.
[34]	Ferrari R, Grassi M, Salvi E, Borroni B, Palluzzi F, Pepe D, D'Avila F, Padovani A, Archetti S, Rainero I, Rubino E, Pinessi L, Benussi L, Binetti G, Ghidoni R, Galimberti D, Scarpini E, Serpente M, Rossi G, Giaccone G, Tagliavini F, Nacmias B, Piaceri I, Bagnoli S, Bruni AC, Maletta RG, Bernardi L, Postiglione A, Milan G, Franceschi M, Puca AA, Novelli V, Barlassina C, Glorioso N, Manunta P, Singleton A, Cusi D, Hardy J, Momeni P . Agenome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia. Neurobiol Aging, 2015, 36(10): 2904. e13-26.
[35]	Lewis BP, Burge CB, Bartel DP . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005,120(1):15-20.
[36]	Bhattacharya A, Cui Y . Knowledge-based analysis of functional impacts of mutations in microRNA seed regions. J Biosci, 2015,40(4):791-798.
[37]	Mencia A, Modamio-Høybjør S, Redshaw N, Morín M, Mayo-Merino F, Olavarrieta L, Aguirre LA, del Castillo I, Steel KP, Dalmay T, Moreno F, Moreno-Pelayo MA . Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat Genet, 2009,41(5):609-613.
[38]	Iliff BW, Riazuddin SA, Gottsch JD . A single-base substitution in the seed region of miR-184 causes EDICT syndrome. Invest Ophth Vis Sci, 2012,53(1):348-353.
[39]	Jiang Q, Zhao H, Li R, Zhang Y, Liu Y, Wang J, Wang X, Ju Z, Liu W, Hou M, Huang J . In silico genome-wide miRNA-QTL-SNPs analyses identify a functional SNP associated with mastitis in Holsteins. BMC Genet, 2019,20(1):46.
[40]	Chai J, Chen L, Luo Z, Zhang T, Chen L, Lou P, Sun W, Long X, Lan J, Wang J, Pu H, Qiu J, Shuai S, Guo Z . Spontaneous single nucleotide polymorphism in porcine microRNA-378 seed region leads to functional alteration. Biosci Biotechnol Biochem, 2018,82(7):1081-1089.
[41]	Richardson K, Lai CQ, Parnell LD, Lee YC, Ordovas JM . A genome-wide survey for SNPs altering microRNA seed sites identifies functional candidates in GWAS. BMC Genomics, 2011,12:504.
[42]	Hou Y, Liang W, Zhang J, Li Q, Ou H, Wang Z, Li S, Huang X, Zhao C . Schizophrenia-associated rs4702 G allele-specific downregulation of FURIN expression by miR-338-3p reduces BDNF production. Schizophr Res, 2018,199:176-180.
[43]	Rossi M, Kilpinen H, Muona M, Surakka I, Ingle C, Lahtinen J, Hennah W, Ripatti S, Hovatta I . Allele-specific regulation of DISC1 expression by miR-135b-5p. Eur J Hum Genet, 2014,22(6):840-843.
[44]	Hauberg ME, Roussos P, Grove J, Børglum AD, Mattheisen M , Schizophrenia Working Group of the Psychiatric Genomics Consortium. Analyzing the Role of MicroRNAs in schizophrenia in the context of common genetic risk variants. JAMA Psychiat, 2016,73(4):369-377.
[45]	Manley W, Moreau MP, Azaro M, Siecinski SK, Davis G, Buyske S, Vieland V, Bassett AS, Brzustowicz L . Validation of a microRNA target site polymorphism in H3F3B that is potentially associated with a broad schizophrenia phenotype. PLoS One, 2018,13(3):e0194233.
[46]	John J, Bhatia T, Kukshal P, Chandna P, Nimgaonkar VL, Deshpande SN, Thelma BK . Association study of MiRSNPs with schizophrenia, tardive dyskinesia and cognition. Schizophr Res, 2016,174(1-3):29-34.
[47]	Wu S, Zhang R, Nie F, Wang X, Jiang C, Liu M, Valenzuela RK, Liu W, Shi Y, Ma J . MicroRNA-137 Inhibits EFNB2 expression affected by a genetic variant and is expressed aberrantly in peripheral blood of schizophrenia patients. E Bio Medicine, 2016,12:133-142.
[48]	Agarwal V, Bell GW, Nam JW, Bartel DP . Predicting effective microRNA target sites in mammalian mRNAs. eLife, 2015,4.
[49]	Betel D, Koppal A, Agius P, Sander C, Leslie C . Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol, 2010,11(8):R90.
[50]	Sticht C, De La Torre C, Parveen A, Gretz N . MiRWalk: an online resource for prediction of microRNA binding sites. PLoS One, 2018,13(10):e0206239.
[51]	Kozomara A, Birgaoanu M, Griffiths-Jones S . MiRBase: from microRNA sequences to function. Nucleic Acids Res, 2019,47(D1):D155-D162.
[52]	Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R . Fast and effective prediction of microRNA/target duplexes. RNA, 2004,10(10):1507-1517.
[53]	Gong J, Liu C, Liu W, Wu Y, Ma Z, Chen H, Guo AY . An update of miRNASNP database for better SNP selection by GWAS data, miRNA expression and online tools. Database (Oxford), 2015, 2015: bav029.
[54]	Deveci M, Catalyürek UV, Toland AE . MrSNP: software to detect SNP effects on microRNA binding. BMC Bioinformatics, 2014,15:73.
[55]	Liu C, Zhang F, Li T, Lu M, Wang L, Yue W, Zhang D . MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genomics, 2012,13:661.
[56]	Zorc M, Obsteter J, Dovc P, Kunej T . Genetic variability of MicroRNA genes in 15 animal species. J Genomics, 2015,3:51-56.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号
总访问:,今日访问:,当前在线:

精神分裂症相关单核苷酸多态性调控microRNA功能研究进展

Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	张晴,平杰,张昊翔,康波,李元丰,周钢桥. MKL1基因多态性与高原环境适应性的遗传关联研究[J]. 遗传, 2019, 41(7): 634-643.
[2]	彭哲也,唐紫珺,谢民主. 机器学习方法在基因交互作用探测中的研究进展[J]. 遗传, 2018, 40(3): 218-226.
[3]	刘莉莉, 郭爱伟, 吴培福, 陈粉粉, 杨亚晋, 张勤. 敲降VPS28基因对中国荷斯坦奶牛乳脂合成的调控[J]. 遗传, 2018, 40(12): 1092-1100.
[4]	杨超, 杨瑞馥, 崔玉军. 细菌全基因组关联研究的方法与应用[J]. 遗传, 2018, 40(1): 57-65.
[5]	王钰嫣,王子兴,胡耀达,王蕾,李宁,张彪,韩伟,姜晶梅. 全基因组关联研究通路分析方法现状[J]. 遗传, 2017, 39(8): 707-716.
[6]	杨熳,卢冰婕,段媛媛,陈晓峰,马建岗,郭燕. 骨质疏松症易感基因BDNF的遗传学关联分析及功能研究[J]. 遗传, 2017, 39(8): 726-736.
[7]	张统雨,朱才业,杜立新,赵福平. 羊重要性状全基因组关联分析研究进展[J]. 遗传, 2017, 39(6): 491-500.
[8]	弓弦,张超,伊利亚斯·艾萨,时瑛,杨雪唯,努尔斯曼古丽奥斯曼,关亚群,徐书华. 2型糖尿病易感候选基因在世界不同人群中的多样性比较分析[J]. 遗传, 2016, 38(6): 543-559.
[9]	陈开旭, 王为兰, 张富春, 郑秀芬. 人类身高的遗传学研究进展[J]. 遗传, 2015, 37(8): 741-755.
[10]	汤静思, 杨明耀, 李英. 假基因的功能及其在癌症疾病中的重要作用[J]. 遗传, 2015, 37(1): 8-16.
[11]	王立, 徐颜美, 程竹君, 熊招平, 邓立彬. 胆固醇代谢紊乱的遗传学研究进展[J]. 遗传, 2014, 36(9): 857-863.
[12]	樊春燕, 魏强, 郝志强, 李广林. miRNAs调控lincRNAs的生物信息学预测与功能分析[J]. 遗传, 2014, 36(12): 1226-1234.
[13]	周家蓬裴智勇陈禹保陈润生. 基于高通量测序的全基因组关联研究策略[J]. 遗传, 2014, 36(11): 1099-1111.
[14]	宋庆峰, 张红星, 马亦龙, 周钢桥. 复杂疾病的遗传易感基因区域的精细定位[J]. 遗传, 2014, 36(1): 2-10.
[15]	罗旭红刘志芳董长征. 基因水平的关联分析方法[J]. 遗传, 2013, 35(9): 1065-1071.