title: Molecular network analysis enhances understanding of the biology of mental disorders.
abstract: We provide an introduction to network theory, evidence to support a connection between molecular network structure and neuropsychiatric disease, and examples of how network approaches can expand our knowledge of the molecular bases of these diseases. Without systematic methods to derive their biological meanings and inter-relatedness, the many molecular changes associated with neuropsychiatric disease, including genetic variants, gene expression changes, and protein differences, present an impenetrably complex set of findings. Network approaches can potentially help integrate and reconcile these findings, as well as provide new insights into the molecular architecture of neuropsychiatric diseases. Network approaches to neuropsychiatric disease are still in their infancy, and we discuss what might be done to improve their prospects.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Kay S
authors.initials: KS
authors.lastname: Grennan
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: Chunyu
authors.initials: C
authors.lastname: Liu
mesh_terms: D053263:Gene Regulatory Networks; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D010641:Phenotype
keywords: mental disorders; molecular networks; neuropsychiatric disease; systems biology
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8685-90
references.pmid: 17502601
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10420-5
references.pmid: 22689976
references.citation: Front Neurosci. 2012 Dec 24;6:187
references.pmid: 23269912
references.citation: J Proteome Res. 2013 Jul 5;12(7):3181-92
references.pmid: 23718855
references.citation: Mol Psychiatry. 2013 Dec;18(12):1308-14
references.pmid: 23147385
references.citation: Mol Psychiatry. 2014 Aug;19(8):890-4
references.pmid: 23979604
references.citation: Science. 2010 Jan 22;327(5964):425-31
references.pmid: 20093466
references.citation: Br J Psychiatry. 2009 Aug;195(2):97-9
references.pmid: 19648536
references.citation: Schizophr Bull. 2014 Jan;40(1):39-49
references.pmid: 23671194
references.citation: Mol Syst Biol. 2007;3:89
references.pmid: 17353931
references.citation: Bioessays. 2009 Feb;31(2):220-7
references.pmid: 19204994
references.citation: Neuron. 2011 Jun 9;70(5):898-907
references.pmid: 21658583
references.citation: Nat Rev Genet. 2009 Jun;10(6):392-404
references.pmid: 19434077
references.citation: Mol Psychiatry. 2007 Jan;12(1):74-86
references.pmid: 17043677
references.citation: Nat Neurosci. 2012 Dec;15(12):1723-8
references.pmid: 23143521
references.citation: Nature. 2003 Jul 31;424(6948):549-52
references.pmid: 12891357
references.citation: Cell. 2013 Nov 21;155(5):1008-21
references.pmid: 24267887
references.citation: Am J Hum Genet. 2006 Jun;78(6):1011-25
references.pmid: 16685651
references.citation: Brief Bioinform. 2010 Jan;11(1):15-29
references.pmid: 20061351
references.citation: PLoS Comput Biol. 2013;9(3):e1002975
references.pmid: 23555212
references.citation: Biochem J. 2013 Jun 15;452(3):477-88
references.pmid: 23557398
references.citation: Nat Genet. 2013 Sep;45(9):984-94
references.pmid: 23933821
references.citation: Methods. 2013 Sep 1;63(1):32-40
references.pmid: 23545196
references.citation: Interdiscip Sci. 2013 Jun;5(2):85-94
references.pmid: 23740389
references.citation: Am J Psychiatry. 2013 May;170(5):521-32
references.pmid: 23511790
references.citation: Cell. 2013 Apr 25;153(3):654-65
references.pmid: 23622248
references.citation: Pharmacogenomics. 2012 Jan;13(2):213-22
references.pmid: 22256870
references.citation: Nat Rev Genet. 2012 Jul 10;13(8):537-51
references.pmid: 22777127
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17973-8
references.pmid: 17101986
references.citation: PLoS Genet. 2013 Jun;9(6):e1003523
references.pmid: 23754953
references.citation: Twin Res Hum Genet. 2012 Jun;15(3):336-50
references.pmid: 22856369
references.citation: IEEE/ACM Trans Comput Biol Bioinform. 2010 Apr-Jun;7(2):208-17
references.pmid: 20431141
references.citation: Nat Biotechnol. 2011 Jun 01;29(7):607-14
references.pmid: 21633356
references.citation: Nature. 2000 Jul 27;406(6794):378-82
references.pmid: 10935628
references.citation: PLoS One. 2013 Apr 17;8(4):e61505
references.pmid: 23613865
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1193-8
references.pmid: 22223662
references.citation: Trends Genet. 2013 Jul;29(7):384
references.pmid: 23746964
references.citation: Nat Genet. 2011 Sep 18;43(10):969-76
references.pmid: 21926974
references.citation: Bioessays. 2009 Oct;31(10):1110-5
references.pmid: 19722183
references.citation: Cell. 2013 Nov 21;155(5):997-1007
references.pmid: 24267886
references.citation: J Psychiatr Res. 2013 Sep;47(9):1215-21
references.pmid: 23786914
references.citation: J Vis Exp. 2011 Apr 30;(50):
references.pmid: 21559008
references.citation: Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12253-8
references.pmid: 23836637
references.citation: PLoS Comput Biol. 2012;8(9):e1002690
references.pmid: 23028288
references.citation: PLoS Comput Biol. 2012;8(3):e1002444
references.pmid: 22479173
references.citation: Eur J Hum Genet. 2013 Jan;21(1):95-101
references.pmid: 22713803
references.citation: Mol Biosyst. 2009 Dec;5(12):1482-93
references.pmid: 20023717
references.citation: Am J Hum Genet. 2005 Sep;77(3):377-88
references.pmid: 16080114
references.citation: Nature. 2012 Sep 6;489(7414):91-100
references.pmid: 22955619
references.citation: J Am Med Inform Assoc. 2013 Dec;20(e2):e297-305
references.pmid: 23956017
references.citation: Nat Methods. 2011 Jun;8(6):478-80
references.pmid: 21516116
references.citation: Eur Rev Med Pharmacol Sci. 2013 Jul;17(14):1874-80
references.pmid: 23877850
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D92-7
references.pmid: 24297251
references.citation: Front Genet. 2013 May 17;4:87
references.pmid: 23730306
references.citation: Science. 1995 Oct 20;270(5235):467-70
references.pmid: 7569999
references.citation: Sci Transl Med. 2011 Jun 8;3(86):86ra49
references.pmid: 21653829
references.citation: Nature. 2011 May 25;474(7351):380-4
references.pmid: 21614001
references.citation: Nat Rev Genet. 2004 Nov;5(11):826-37
references.pmid: 15520792
references.citation: Nat Rev Mol Cell Biol. 2010 Nov;11(11):764-76
references.pmid: 20966970
references.citation: Eur J Hum Genet. 2009 Oct;17(10):1231-40
references.pmid: 19277065
references.citation: BMC Bioinformatics. 2005 Sep 14;6:227
references.pmid: 16162296
references.citation: Biol Psychiatry. 2014 Mar 1;75(5):351-60
references.pmid: 23992925
references.citation: PLoS Comput Biol. 2010 Jan 15;6(1):e1000641
references.pmid: 20090828
references.citation: Nature. 2012 Sep 6;489(7414):57-74
references.pmid: 22955616
references.citation: PLoS Biol. 2008 Nov 4;6(11):e264
references.pmid: 18986213
references.citation: Cell. 2013 Aug 1;154(3):518-29
references.pmid: 23911319
references.citation: Genome Biol. 2011 Jun 17;12(6):306
references.pmid: 21682935
references.citation: BMC Bioinformatics. 2006 Jan 06;7:3
references.pmid: 16398926
references.citation: J Comput Biol. 2009 Feb;16(2):181-9
references.pmid: 19193144
references.citation: Genome Res. 2011 Jul;21(7):1109-21
references.pmid: 21536720
references.citation: PLoS One. 2013 May 03;8(5):e62670
references.pmid: 23658761
references.citation: Nature. 1989 Jul 20;340(6230):245-6
references.pmid: 2547163
references.citation: Neurobiol Aging. 2009 Sep;30(9):1333-49
references.pmid: 18206267
references.citation: Nature. 2008 Sep 4;455(7209):58-63
references.pmid: 18668040
references.citation: Methods Cell Biol. 2012;110:19-56
references.pmid: 22482944
references.citation: Nat Biotechnol. 2007 Mar;25(3):309-16
references.pmid: 17344885
references.citation: Future Virol. 2012 Sep;7(9):885-899
references.pmid: 23335944
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12698-703
references.pmid: 20616000
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1047-55
references.pmid: 18228528
references.citation: PLoS One. 2010 Jun 29;5(6):e11351
references.pmid: 20613869
references.citation: PLoS Genet. 2012;8(3):e1002556
references.pmid: 22412387
references.citation: Bioessays. 2002 Mar;24(3):267-74
references.pmid: 11891763
references.citation: Lancet. 2013 Apr 20;381(9875):1371-1379
references.pmid: 23453885
references.citation: Nat Biotechnol. 2009 Feb;27(2):199-204
references.pmid: 19182785
references.citation: Circ Res. 2006 Mar 3;98(4):532-9
references.pmid: 16424366
references.citation: PLoS Genet. 2008 Feb 29;4(2):e1000008
references.pmid: 18454194
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2013 Jan;162B(1):1-16
references.pmid: 23129290
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2012 Sep-Oct;4(5):429-42
references.pmid: 22689539
references.citation: PLoS Comput Biol. 2012;8(2):e1002375
references.pmid: 22383865
references.citation: Stat Appl Genet Mol Biol. 2005;4:Article17
references.pmid: 16646834
references.citation: PLoS Comput Biol. 2013;9(1):e1002860
references.pmid: 23300433
references.citation: Int J Methods Psychiatr Res. 2014 Jan;23 Suppl 1:92-101
references.pmid: 24375537
references.citation: J Vis Exp. 2010 Jul 02;(41):
references.pmid: 20644507
references.citation: Am J Psychiatry. 2013 Nov;170(11):1263-74
references.pmid: 23846857
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11694-9
references.pmid: 17609372
references.citation: Am J Hum Genet. 2008 Apr;82(4):949-58
references.pmid: 18371930
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8089-96; discussion 8086-8
references.pmid: 15863612
references.citation: Bioinformatics. 2009 Feb 15;25(4):526-32
references.pmid: 19112081
references.citation: Genome Biol. 2009;10(5):R55
references.pmid: 19463160
references.citation: Am J Psychiatry. 2003 Apr;160(4):636-45
references.pmid: 12668349
references.citation: Bioinformatics. 2011 Sep 1;27(17):2414-21
references.pmid: 21798963
references.citation: Genetics. 2010 Nov;186(3):767-73
references.pmid: 21062962
references.citation: BMC Bioinformatics. 2011;12 Suppl 13:S20
references.pmid: 22373040
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4323-8
references.pmid: 18326631
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D841-4
references.pmid: 23193266
references.citation: Nat Rev Genet. 2011 Mar;12(3):204-13
references.pmid: 21331091
references.citation: Hum Hered. 2003;56(1-3):73-82
references.pmid: 14614241
references.citation: Eur J Hum Genet. 2005 Jul;13(7):807-14
references.pmid: 15841096
references.citation: Sci Rep. 2012;2:691
references.pmid: 23056904
references.citation: Nat Methods. 2013 Apr;10(4):339-42
references.pmid: 23455924
references.citation: PLoS Genet. 2011 Aug;7(8):e1002237
references.pmid: 21876681
references.citation: Hum Mol Genet. 2000 May 22;9(9):1415-23
references.pmid: 10814723
references.citation: PLoS Comput Biol. 2010 Jan 15;6(1):e1000642
references.pmid: 20090830
references.citation: Cell. 2013 Apr 25;153(3):707-20
references.pmid: 23622250
references.citation: Genome Res. 2010 Aug;20(8):1143-53
references.pmid: 20538624
references.citation: Schizophr Res. 2013 Jan;143(1):55-9
references.pmid: 23153825
references.citation: BMC Syst Biol. 2011;5 Suppl 3:S12
references.pmid: 22784618
references.citation: Genetics. 2012 Mar;190(3):1131-7
references.pmid: 22214609