A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

doi:10.1038/ncomms14972

GSTDTAP > 资源环境科学

DOI	10.1038/ncomms14972
	A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
	Madireddy, Lohith 1; 39;Alfonso, Sandra 2
	2019-05-20
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2019
卷号	10
文章类型	Article
语种	英语
国家	USA; Norway; Germany; Italy; Australia; Spain; England; Canada; Greece; France; Belgium; Cyprus; Netherlands; Czech Republic; Japan; Austria; Sweden; Switzerland; Denmark; Finland
英文摘要	Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000468275100001
WOS关键词	GENOME-WIDE ASSOCIATION ; POLYGENIC RISK SCORE ; GWAS ; EXPRESSION ; CYTOSCAPE ; PATHWAY
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/203278
专题	资源环境科学
作者单位	1.Univ Calif San Francisco, Weill Inst Neurosci, Dept Neurol, San Francisco, CA 94158 USA; 2.Harvard Med Sch, Syst Biol & Comp Sci Program, Ann Romney Ctr Neurol Dis, Dept Neurol,Brigham & Womens Hosp, Boston, MA 02115 USA; 3.Harvard Med Sch, Div Genet, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA; 4.Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA 02142 USA; 5.Yale Sch Med, Dept Neurol, 300 George St, New Haven, CT 06511 USA; 6.Yale Sch Med, Dept Genet, 300 George St, New Haven, CT 06511 USA; 7.Univ Oslo, Inst Clin Med, N-0318 Oslo, Norway; 8.Oslo Univ Hosp, Dept Neurol, N-0424 Oslo, Norway; 9.Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA; 10.Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn Dept Human Genet, Miami, FL 33136 USA; 11.Tech Univ Munich, Dept Neurol, Klinikum Rechts Isar, Sch Med, D-81675 Munich, Germany; 12.Munich Cluster Syst Neurol SyNergy, D-81377 Munich, Germany; 13.Univ Calif Berkeley, Div Epidemiol, Sch Publ Hlth, 324 Stanley Hall,MC 3220, Berkeley, CA 94720 USA; 14.Oslo Metropolitan Univ, Dept Mech Elect & Chem Engn, N-0167 Oslo, Norway; 15.Univ Pavia, Sect Biostat Neurophyisiol & Psychiat, Unit Med & Genom Stat, I-27100 Pavia, Italy; 16.Univ Milan, Dept Biomed Sci Hlth, I-20133 Milan, Italy; 17.IRCCS Policlin San Donato, MS Res Unit, I-20097 Milan, Italy; 18.IRCCS Policlin San Donato, Dept Neurol, I-20097 Milan, Italy; 19.Westmead Inst Med Res, Fac Med, Westmead Clin Sch, Sydney, NSW 2145, Australia; 20.Case Western Reserve Univ, Sch Med, Dept Quantitat & Populat Hlth Sci, Cleveland, OH 44106 USA; 21.Univ Oslo, Inst Hlth & Soc, N-0318 Oslo, Norway; 22.Univ Autonoma Barcelona, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya Cemcat, Inst Recerca Vall dHebron VHIR,Hosp Univ Vall dHe, Barcelona 08035, Spain; 23.Ist Sci San Raffaele, Dept Neurol, I-20132 Milan, Italy; 24.UPO Univ, Dept Hlth Sci, I-28100 Novara, Italy; 25.Univ Cambridge, Dept Clin Neurosci, Neurol Unit, Cambridge CB2 1QW, England; 26.Univ Montreal, Fac Med, MS Clin Ctr Hosp 1, Montreal, PQ H3A 1G1, Canada; 27.Univ Thessaly, Dept Neurol, Neurogenet Lab, Univ Hosp Larissa, Larisa 41223, Greece; 28.Univ Hop Pitie Salpetriere, Dept Neurol, F-75013 Paris, France; 29.Sorbonne Univ, UMR 1127, INSERM, Univ Hop Pitie Salpetriere, F-75013 Paris, France; 30.Katholieke Univ Leuven, Dept Neurosci, Lab Neuroimmunol, B-3000 Leuven, Belgium; 31.Univ Nantes, Ctr Rech Transplantat & Immunol, INSERM, UMR 1064,ATIP Avenir,Equipe 5, F-44093 Nantes, France; 32.CHU Nantes, INSERM, Pole Hosp Univ 11, CIC 1413,Sante Publ,Clin Donnees, F-44093 Nantes, France; 33.Univ Cyprus, Dept Neurol, Sch Med, 587G X2, Nicosia, Cyprus; 34.Keele Univ, Inst Sci & Technol Med, Keele ST5 5GB, Staffs, England; 35.Erasmus MC, Dept Neurol, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands; 36.Erasmus MC, Dept Immunol, NL-3015 GD Rotterdam, Netherlands; 37.Charles Univ Prague, Fac Med 1, Dept Neurol, 3CFG RJ, Prague, Czech Republic; 38.Charles Univ Prague, Ctr Clin Neurosci, 3CFG RJ, Prague, Czech Republic; 39.Gen Univ Hosp, 3CFG RJ, Prague, Czech Republic; 40.Kyushu Univ, Dept Neurol, Kyushu 8120053, Japan; 41.Univ Hosp North Midlands, Royal Stoke MS Ctr Excellence, Stoke On Trent ST4 6QG, Staffs, England; 42.Med Univ Graz, Dept Neurol, A-8036 Graz, Austria; 43.Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden; 44.Karolinska Inst, Ctr Mol Med, S-17176 Stockholm, Sweden; 45.Johannes Gutenberg Univ Mainz, Dept Neurol, Univ Med Ctr, D-55131 Mainz, Germany; 46.Univ Lubeck, Genet & Mol Epidemiol Grp, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet, D-23562 Lubeck, Germany; 47.Univ Lubeck, Genet & Mol Epidemiol Grp, Lubeck Interdisciplinary Platform Genome Analyt, Inst Cardiogenet, D-23562 Lubeck, Germany; 48.Univ Zurich, Neuroimmunol & MS Res Nims, Dept Neurol, CH-8006 Zurich, Switzerland; 49.Univ Copenhagen, Dept Neurol, Sect 2082, Rigshosp,Danish Multiple Sclerosis Ctr, DK-2100 Copenhagen, Denmark; 50.Univ Helsinki, Inst Mol Med Finland FIMM, FIN-00014 Helsinki, Finland; 51.Harvard Univ, Ctr Human Genet Res, Boston, MA 02115 USA; 52.UCL, UK Dementia Res Inst, London WC1E 6BT, England; 53.Univ Tasmania, Menzies Inst Med Res, Hobart, Tas 7000, Australia; 54.Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge CB2 0QQ, England; 55.Columbia Univ, Dept Neurol, Med Ctr, Ctr Translat & Computat Neuroimmunol, New York, NY 10032 USA; 56.Columbia Univ, Multiple Sclerosis Ctr, Med Ctr, New York, NY 10032 USA; 57.Univ Calif San Francisco, Bakar Inst Computat Hlth Sci, San Francisco, CA 94158 USA
推荐引用方式 GB/T 7714	Madireddy, Lohith,39;Alfonso, Sandra. A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis[J]. NATURE COMMUNICATIONS,2019,10.
APA	Madireddy, Lohith,&39;Alfonso, Sandra.(2019).A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.NATURE COMMUNICATIONS,10.
MLA	Madireddy, Lohith,et al."A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis".NATURE COMMUNICATIONS 10(2019).