title: Genetic psychophysiology: advances, problems, and future directions.
abstract: This paper presents an overview of historical advances and the current state of genetic psychophysiology, a rapidly developing interdisciplinary research linking genetics, brain, and human behavior, discusses methodological problems, and outlines future directions of research. The main goals of genetic psychophysiology are to elucidate the neural pathways and mechanisms mediating genetic influences on cognition and emotion, identify intermediate brain-based phenotypes for psychopathology, and provide a functional characterization of genes being discovered by large association studies of behavioral phenotypes. Since the initiation of this neurogenetic approach to human individual differences in the 1970s, numerous twin and family studies have provided strong evidence for heritability of diverse aspects of brain function including resting-state brain oscillations, functional connectivity, and event-related neural activity in a variety of cognitive and emotion processing tasks, as well as peripheral psychophysiological responses. These data indicate large differences in the presence and strength of genetic influences across measures and domains, permitting the selection of heritable characteristics for gene finding studies. More recently, candidate gene association studies began to implicate specific genetic variants in different aspects of neurocognition. However, great caution is needed in pursuing this line of research due to its demonstrated proneness to generate false-positive findings. Recent developments in methods for physiological signal analysis, hemodynamic imaging, and genomic technologies offer new exciting opportunities for the investigation of the interplay between genetic and environmental factors in the development of individual differences in behavior, both normal and abnormal.
authors.affiliation: Washington University School of Medicine, Department of Psychiatry, 660 S. Euclid, Box 8134, St. Louis, MO 63110, United States. Electronic address: andrey@wustl.edu.
authors.forename: Andrey P
authors.initials: AP
authors.lastname: Anokhin
mesh_terms: D001921:Brain / Q000502:physiology*; D058256:Brain Waves / Q000235:genetics*; D008040:Genetic Linkage; D005823:Genetics; D006801:Humans; D011603:Psychophysiology; D018433:Twin Studies as Topic
keywords: Brain; EEG; ERP; Endophenotype; Genetics; Heritability
references.citation: Arch Gen Psychiatry. 1990 Feb;47(2):181-8
references.pmid: 2405807
references.citation: Crit Rev Neurobiol. 2000;14(3-4):199-224
references.pmid: 12645958
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
references.pmid: 11549226
references.citation: Behav Genet. 2007 Mar;37(2):302-13
references.pmid: 17180712
references.citation: PLoS One. 2012;7(9):e46289
references.pmid: 23050006
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2003 Feb;117B(1):51-6
references.pmid: 12555235
references.citation: Nat Rev Genet. 2012 Sep;13(9):640-53
references.pmid: 22847273
references.citation: Biol Psychol. 1998 Feb;47(2):97-120
references.pmid: 9554183
references.citation: Neurosci Biobehav Rev. 2011 May;35(6):1363-96
references.pmid: 21382410
references.citation: BMC Med Genet. 2010 Mar 18;11:43
references.pmid: 20298578
references.citation: Genomics. 1992 Jan;12(1):69-73
references.pmid: 1346390
references.citation: Am J Hum Genet. 2012 Jan 13;90(1):7-24
references.pmid: 22243964
references.citation: Arch Gen Psychiatry. 2002 Dec;59(12):1085-96
references.pmid: 12470124
references.citation: Hum Genet. 1988 Oct;80(2):165-76
references.pmid: 3169741
references.citation: Clin Neurophysiol. 2005 Oct;116(10):2266-301
references.pmid: 16115797
references.citation: Neuropsychopharmacology. 2004 Aug;29(8):1506-11
references.pmid: 15187981
references.citation: Front Hum Neurosci. 2013 Mar 11;7:76
references.pmid: 23482840
references.citation: Neurosci Lett. 2003 Dec 15;353(1):45-8
references.pmid: 14642434
references.citation: BMC Neurosci. 2011 Apr 20;12:33
references.pmid: 21507249
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3729-33
references.pmid: 11891318
references.citation: Biol Psychiatry. 1999 Oct 1;46(7):970-81
references.pmid: 10509180
references.citation: Biol Psychiatry. 1996 Feb 15;39(4):289-95
references.pmid: 8645776
references.citation: Brain Topogr. 2012 Oct;25(4):431-42
references.pmid: 22562716
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11073-8
references.pmid: 17576922
references.citation: JAMA. 2009 Jan 21;301(3):304-8
references.pmid: 19155457
references.citation: Psychophysiology. 2003 Sep;40(5):727-41
references.pmid: 14696726
references.citation: Biol Psychol. 2004 Oct;67(1-2):157-82
references.pmid: 15130530
references.citation: Biol Psychiatry. 2002 Apr 15;51(8):621-31
references.pmid: 11955462
references.citation: Conscious Cogn. 2005 Jun;14(2):390-425
references.pmid: 15950889
references.citation: Ann Hum Genet. 1981 Feb;45(1):15-9
references.pmid: 7316475
references.citation: Alcohol Clin Exp Res. 1995 Jun;19(3):567-76
references.pmid: 7573776
references.citation: Biol Psychol. 2009 Dec;82(3):199-210
references.pmid: 19576948
references.citation: Behav Genet. 2001 Nov;31(6):637-51
references.pmid: 11838540
references.citation: Dev Psychobiol. 2014 Jan;56(1):73-85
references.pmid: 23168718
references.citation: Curr Psychiatry Rep. 2003 Jun;5(2):155-61
references.pmid: 12685995
references.citation: Eur Arch Psychiatry Neurol Sci. 1988;237(4):244-52
references.pmid: 3203702
references.citation: Ann Neurol. 2008 Oct;64(4):455-60
references.pmid: 18688819
references.citation: Biol Psychiatry. 1998 Jan 1;43(1):40-51
references.pmid: 9442343
references.citation: Hum Genet. 1992 Sep-Oct;90(1-2):99-112
references.pmid: 1427795
references.citation: Biol Psychol. 2002 Oct;61(1-2):229-48
references.pmid: 12385677
references.citation: Electroencephalogr Clin Neurophysiol. 1996 Jun;98(6):502-14
references.pmid: 8763510
references.citation: Mol Psychiatry. 2000 Jan;5(1):11-3
references.pmid: 10673763
references.citation: Nat Rev Neurosci. 2002 Mar;3(3):201-15
references.pmid: 11994752
references.citation: Brain Topogr. 1993 Spring;5(3):241-51
references.pmid: 8507550
references.citation: Biol Psychol. 2004 Oct;67(1-2):183-218
references.pmid: 15130531
references.citation: Biol Psychol. 2004 Oct;67(1-2):1-5
references.pmid: 15130523
references.citation: Arch Gen Psychiatry. 2011 Aug;68(8):773-80
references.pmid: 21464342
references.citation: Psychol Med. 2007 Feb;37(2):163-80
references.pmid: 16978446
references.citation: Psychophysiology. 2009 Sep;46(5):962-9
references.pmid: 19558402
references.citation: Neuroscience. 2011 Apr 28;180:148-56
references.pmid: 21315807
references.citation: Brain Cogn. 1995 Apr;27(3):353-97
references.pmid: 7626281
references.citation: Cogn Affect Behav Neurosci. 2003 Mar;3(1):17-26
references.pmid: 12822595
references.citation: Am J Hum Genet. 2004 Apr;74(4):705-14
references.pmid: 15024690
references.citation: Science. 1982 Dec 17;218(4578):1235-7
references.pmid: 7146906
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17798-803
references.pmid: 16314575
references.citation: Eur Arch Psychiatry Clin Neurosci. 2004 Jun;254(3):190-8
references.pmid: 15205974
references.citation: J Neurosci. 2005 Nov 2;25(44):10131-7
references.pmid: 16267220
references.citation: Am J Hum Genet. 1996 Mar;58(3):562-73
references.pmid: 8644716
references.citation: Clin Trials. 2007;4(3):245-53
references.pmid: 17715249
references.citation: Twin Res Hum Genet. 2006 Jun;9(3):343-59
references.pmid: 16790145
references.citation: Psychophysiology. 2009 Jul;46(4):787-96
references.pmid: 19386046
references.citation: Hum Brain Mapp. 2005 Nov;26(3):191-8
references.pmid: 15929086
references.citation: Alcohol. 2010 Jun;44(4):335-42
references.pmid: 20598842
references.citation: Hum Genet. 1979 Feb 28;47(1):1-45
references.pmid: 570956
references.citation: Nature. 2009 Jan 22;457(7228):475-9
references.pmid: 19158795
references.citation: Methods Mol Biol. 2013;1019:215-36
references.pmid: 23756893
references.citation: Annu Rev Clin Psychol. 2008;4:325-48
references.pmid: 18370620
references.citation: Int J Psychophysiol. 2009 Jul;73(1):17-21
references.pmid: 19530275
references.citation: Hum Neurobiol. 1986;5(1):49-58
references.pmid: 3700148
references.citation: Act Nerv Super (Praha). 1978 Feb;20(1):48-9
references.pmid: 565122
references.citation: Biol Psychol. 2010 Dec;85(3):504-8
references.pmid: 20920548
references.citation: Prog Exp Pers Psychopathol Res. 1993;16:163-99
references.pmid: 8293080
references.citation: Psychophysiology. 2007 Jan;44(1):106-12
references.pmid: 17241146
references.citation: Biol Psychol. 2007 May;75(2):154-64
references.pmid: 17316957
references.citation: Humangenetik. 1970 Sep 17;10(2):91-114
references.pmid: 5528299
references.citation: Am J Med Genet. 1995 Oct 9;60(5):400-8
references.pmid: 8546153
references.citation: Clin Neurophysiol. 2012 Mar;123(3):424-58
references.pmid: 22169062
references.citation: Twin Res Hum Genet. 2007 Apr;10(2):335-47
references.pmid: 17564523
references.citation: Neuropsychopharmacology. 2004 Nov;29(11):1943-61
references.pmid: 15305167
references.citation: Biol Psychol. 1997 Oct 10;46(3):235-46
references.pmid: 9360775
references.citation: Biol Cybern. 1995 Oct;73(5):477-82
references.pmid: 7578482
references.citation: Psychophysiology. 1994 Sep;31(5):495-502
references.pmid: 7972604
references.citation: Genet Epidemiol. 1999;17 Suppl 1:S37-42
references.pmid: 10597409
references.citation: Alcohol Res. 2012;34(3):336-8
references.pmid: 23134049
references.citation: Physiol Rev. 1990 Jan;70(1):1-41
references.pmid: 2404287
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):587-92
references.pmid: 9012828
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):359-68
references.pmid: 18618593
references.citation: Schizophr Res. 2007 Jan;89(1-3):312-9
references.pmid: 17014995
references.citation: Biol Psychol. 2010 Feb;83(2):153-8
references.pmid: 20025927
references.citation: Alcohol Clin Exp Res. 2003 May;27(5):765-72
references.pmid: 12766620
references.citation: Psychol Bull. 1994 Jan;115(1):55-73
references.pmid: 8310100
references.citation: Clin Neurophysiol. 2007 Oct;118(10):2128-48
references.pmid: 17573239
references.citation: J Neurosci. 2007 Dec 12;27(50):13882-9
references.pmid: 18077700
references.citation: Genes Brain Behav. 2012 Aug;11(6):712-9
references.pmid: 22554406
references.citation: Psychophysiology. 2012 Feb;49(2):248-51
references.pmid: 22092064
references.citation: Neuropsychol Rev. 2003 Sep;13(3):113-43
references.pmid: 14584908
references.citation: Biol Psychol. 2002 Oct;61(1-2):1-10
references.pmid: 12385666
references.citation: Hum Hered. 2008;66(2):67-86
references.pmid: 18382087
references.citation: Ann N Y Acad Sci. 2010 Mar;1191:133-55
references.pmid: 20392279
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):122-36
references.pmid: 23355297
references.citation: Clin Neurophysiol. 2009 Nov;120(11):1883-1908
references.pmid: 19796989
references.citation: PLoS Comput Biol. 2009 Mar;5(3):e1000314
references.pmid: 19300473
references.citation: Neuropsychobiology. 1996;33(3):113-7
references.pmid: 8776738
references.citation: Int J Psychophysiol. 2004 Jul;53(2):75-90
references.pmid: 15210286
references.citation: Nat Rev Genet. 2002 Nov;3(11):872-82
references.pmid: 12415317
references.citation: JAMA. 2009 Jan 7;301(1):74-81
references.pmid: 19126812
references.citation: Alcohol Clin Exp Res. 1996 Dec;20(9):1523-7
references.pmid: 8986198
references.citation: Alcohol. 1987 Jul-Aug;4(4):249-53
references.pmid: 3620092
references.citation: Int J Psychophysiol. 2003 May;48(2):147-78
references.pmid: 12763572
references.citation: Biol Psychol. 1974;1(4):245-59
references.pmid: 4473236
references.citation: PLoS One. 2012;7(7):e39434
references.pmid: 22802938
references.citation: Clin Neurophysiol. 2009 Jan;120(1):93-107
references.pmid: 19046929
references.citation: Biol Psychiatry. 2006 Jul 15;60(2):141-51
references.pmid: 16476412
references.citation: Behav Genet. 1998 Jan;28(1):9-19
references.pmid: 9573642
references.citation: Biol Psychol. 2013 Sep;94(1):198-209
references.pmid: 23735707
references.citation: Psychophysiology. 1997 Jan;34(1):47-58
references.pmid: 9009808
references.citation: Alcohol Alcohol. 1990;25(2-3):251-6
references.pmid: 2198039
references.citation: Neuropsychopharmacology. 2010 Jan;35(1):301-16
references.pmid: 19693003
references.citation: Electroencephalogr Clin Neurophysiol Suppl. 1995;44:450-9
references.pmid: 7649055
references.citation: Mol Psychiatry. 2009 Feb;14(2):119-20
references.pmid: 19156153
references.citation: Neurosci Biobehav Rev. 2012 Jan;36(1):572-603
references.pmid: 21964481
references.citation: Am J Hum Genet. 1994 Apr;54(4):658-68
references.pmid: 8128963
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10604-9
references.pmid: 16009939
references.citation: Am J Psychiatry. 2011 Oct;168(10):1041-9
references.pmid: 21890791
references.citation: Z Mensch Vererb Konstitutionsl. 1963 Sep 26;37:128-72
references.pmid: 14090268
references.citation: Nat Genet. 2009 Feb;41(2):240-5
references.pmid: 19151718
references.citation: Drug Alcohol Depend. 1997 Jan 10;44(1):1-10
references.pmid: 9031815
references.citation: Neurosci Lett. 2006 Apr 10-17;397(1-2):93-8
references.pmid: 16442730
references.citation: Behav Genet. 2006 Nov;36(6):845-57
references.pmid: 16826459
references.citation: Int J Psychophysiol. 2007 Jan;63(1):3-15
references.pmid: 17129626
references.citation: Neuroscientist. 2005 Dec;11(6):563-76
references.pmid: 16282597
references.citation: Nat Rev Genet. 2005 Feb;6(2):109-18
references.pmid: 15716907
references.citation: Biol Psychiatry. 2000 Aug 15;48(4):265-75
references.pmid: 10960157
references.citation: Prog Brain Res. 2011;193:51-61
references.pmid: 21854955
references.citation: Alcohol Clin Exp Res. 1988 Aug;12(4):545-54
references.pmid: 3056076
references.citation: J Neurosci. 2010 Aug 11;30(32):10727-33
references.pmid: 20702703
references.citation: Behav Genet. 2001 Nov;31(6):545-54
references.pmid: 11838532
references.citation: Psychophysiology. 2009 Jul;46(4):874-9
references.pmid: 19473303
references.citation: Psychol Sci. 2009 Jul;20(7):831-7
references.pmid: 19493320
references.citation: Alcohol Clin Exp Res. 2005 Nov;29(11):2029-38
references.pmid: 16340461
references.citation: Biol Psychiatry. 1993 Mar 1;33(5):335-44
references.pmid: 8471691
references.citation: Science. 1965 Nov 26;150(3700):1187-8
references.pmid: 5852977
references.citation: Biol Psychol. 2002 Oct;61(1-2):33-51
references.pmid: 12385668
references.citation: Biol Psychiatry. 1997 May 15;41(10):1035-44
references.pmid: 9129784
references.citation: JAMA. 2009 Jan 14;301(2):191-7
references.pmid: 19141767
references.citation: Nat Rev Genet. 2005 Feb;6(2):95-108
references.pmid: 15716906
references.citation: Neurosci Lett. 2004 Sep 30;368(3):314-8
references.pmid: 15364418
references.citation: Hum Genet. 1979 Feb 28;47(1):47-80
references.pmid: 429013
references.citation: J Abnorm Psychol. 2009 Feb;118(1):117-30
references.pmid: 19222319
references.citation: Arch Gen Psychiatry. 2004 Feb;61(2):119-29
references.pmid: 14757588
references.citation: Psychophysiology. 2005 Sep;42(5):604-10
references.pmid: 16176383
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):336-43
references.pmid: 16649211
references.citation: Genome Med. 2010 Sep 07;2(9):63
references.pmid: 20828426
references.citation: Lancet. 2013 Apr 20;381(9875):1371-1379
references.pmid: 23453885
references.citation: PLoS One. 2012;7(8):e44154
references.pmid: 22952909
references.citation: Psychophysiology. 1998 Sep;35(5):607-14
references.pmid: 9715104
references.citation: Nat Neurosci. 2012 Sep;15(9):1298-306
references.pmid: 22842146
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2011 Jan;156B(1):44-58
references.pmid: 21184583
references.citation: Psychopharmacology (Berl). 2000 May;149(4):409-13
references.pmid: 10867969
references.citation: Epigenetics. 2010 Aug 16;5(6):516-26
references.pmid: 20505345
references.citation: Nat Rev Genet. 2008 May;9(5):356-69
references.pmid: 18398418
references.citation: N Engl J Med. 2009 Apr 23;360(17):1759-68
references.pmid: 19369657
references.citation: Recent Dev Alcohol. 1991;9:53-67
references.pmid: 1758994
references.citation: Biol Psychol. 2002 Oct;61(1-2):111-38
references.pmid: 12385672
references.citation: Int J Psychophysiol. 2006 Aug;61(2):235-43
references.pmid: 16338015
references.citation: Neuron. 2008 Jun 12;58(5):681-93
references.pmid: 18549781
references.citation: Brain Res. 2011 Mar 4;1377:21-31
references.pmid: 21195697
references.citation: Psychophysiology. 1992 Sep;29(5):576-92
references.pmid: 1410187
references.citation: Behav Genet. 2010 Mar;40(2):186-200
references.pmid: 20155392
references.citation: Behav Genet. 1998 Nov;28(6):443-53
references.pmid: 9926613
references.citation: Biol Psychol. 2007 Jan;74(1):26-33
references.pmid: 16875773
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2003 Apr 1;118B(1):66-71
references.pmid: 12627469
references.citation: Neuropsychopharmacology. 1999 Jul;21(1):51-62
references.pmid: 10379519
references.citation: Proc Natl Acad Sci U S A. 2010 May 11;107(19):8695-700
references.pmid: 20421487
references.citation: Alcohol Clin Exp Res. 1999 Mar;23(3):494-501
references.pmid: 10195824
references.citation: Alcohol. 2009 Feb;43(1):73-84
references.pmid: 19185213
references.citation: Cogn Affect Behav Neurosci. 2012 Jun;12(2):241-68
references.pmid: 22282036
references.citation: Am J Psychiatry. 2003 Apr;160(4):636-45
references.pmid: 12668349
references.citation: Neuroimage. 2009 Jan 1;44(1):265-74
references.pmid: 18793734
references.citation: Behav Genet. 2005 Nov;35(6):695-706
references.pmid: 16273318
references.citation: Biol Psychol. 2013 Feb;92(2):329-41
references.pmid: 23201034
references.citation: Pediatr Res. 2007 May;61(5 Pt 2):38R-42R
references.pmid: 17413848
references.citation: Physiol Rev. 1994 Jan;74(1):1-47
references.pmid: 8295931
references.citation: Behav Genet. 2010 Mar;40(2):167-77
references.pmid: 20111993
references.citation: Biol Psychol. 2002 Oct;61(1-2):203-27
references.pmid: 12385676
references.citation: Hum Genet. 1977 Mar 14;35(3):309-34
references.pmid: 557449
references.citation: Br J Psychiatry. 2010 Oct;197(4):257-8
references.pmid: 20884944
references.citation: Psychiatry Res. 1991 Nov;39(2):181-92
references.pmid: 1798818
references.citation: Hum Brain Mapp. 2008 Dec;29(12):1368-78
references.pmid: 18064590
references.citation: Alcohol Clin Exp Res. 2010 Jun;34(6):988-96
references.pmid: 20374216
references.citation: J Sleep Res. 1999 Jun;8 Suppl 1:11-3
references.pmid: 10389101
references.citation: Psychophysiology. 2008 Jul;45(4):524-34
references.pmid: 18503487
references.citation: Twin Res. 2003 Oct;6(5):361-76
references.pmid: 14624720
references.citation: Electroencephalogr Clin Neurophysiol. 1965 Dec;19(6):570-5
references.pmid: 4158633
references.citation: Science. 2013 Jun 21;340(6139):1467-71
references.pmid: 23722424
references.citation: Curr Opin Neurobiol. 2013 Feb;23(1):57-61
references.pmid: 22878161
references.citation: Psychophysiology. 2007 Jan;44(1):98-105
references.pmid: 17241145
references.citation: Psychophysiology. 1996 Sep;33(5):584-91
references.pmid: 8854746
references.citation: Brief Bioinform. 2002 Jun;3(2):119-33
references.pmid: 12139432
references.citation: Psychophysiology. 2006 Sep;43(5):470-80
references.pmid: 16965609
references.citation: Biol Psychol. 2006 Mar;71(3):289-95
references.pmid: 16054745
references.citation: Alcohol Clin Exp Res. 1999 Jul;23(7):1125-35
references.pmid: 10443977
references.citation: Neuroimage. 2005 Apr 15;25(3):899-915
references.pmid: 15808990
references.citation: Recent Adv Biol Psychiatry. 1966;9:119-30
references.pmid: 4300786
references.citation: Biol Psychiatry. 2002 Jan 1;51(1):59-67
references.pmid: 11801231
references.citation: Physiol Behav. 2002 Dec;77(4-5):477-82
references.pmid: 12526986
references.citation: Behav Genet. 2010 Mar;40(2):178-85
references.pmid: 20127403
references.citation: Annu Rev Genomics Hum Genet. 2012;13:241-61
references.pmid: 22703173
references.citation: Neurobiol Aging. 2012 Apr;33(4):839.e11-21
references.pmid: 22206848
references.citation: Alcohol. 2004 Jun;33(2):99-106
references.pmid: 15528007
references.citation: Biol Psychiatry. 2008 Aug 15;64(4):344-8
references.pmid: 18405882
references.citation: J Neurosci. 2005 Dec 14;25(50):11730-7
references.pmid: 16354931
references.citation: Alcohol Clin Exp Res. 1999 Aug;23(8):1312-9
references.pmid: 10470973