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Participants:Atotalof 825 undergraduates (70.08% females; 29.22%males; mean age= 20.43yo;
87.4% Caucasian,12.6%other) fromaMidwesternUniversitywererecruited fromthePsychology
Department's subject pool.Participants earnedcoursecredit for anhour ofparticipationthat
involved completing self-report questionnaires and donating abuccalcellsamplefor genotyping.The
University’s InstitutionalReview Boardapproved this studyand allparticipants gavewritten
informed consent.
Measures:TheBuss-PerryAggression Questionnaire(BPAQ)was usedto assess thelevels of
aggression byexamining four types:physicalaggression(“I havethreatenedpeopleI know.”),verbal
aggression (“I oftenfind myself disagreeing withpeople”),anger (“Ihavetroublecontrolling my
temper.”),and hostility(“I wonder whysometimes I feelso bitter aboutthings.”).Participants
responded based on a seven-pointcontinuum(1=extremelyuncharacteristicof meto7=extremely
characteristicof me). Atotalscorewas obtained bysummingscores fromallitems (Buss & Perry,
1992).
Genotyping: DNAwas extractedfrombuccalcells using theGentraPURGENECellKit (Qiagen,
Corp,Valencia,CA).HTR1Brs13212041 was genotyped usingTaqman SNP GenotypingAssays
following standard manufacturer protocols (Applied Biosystems,Foster City,CA) in 5uL offinal
solution volume.Genotypes weredetermined usingtheStepOnePlus Real-TimePCR Systemand
endpoint FAM and VIC fluorescentlevels using AB1 SequenceDetection SoftwareV1.2.3.(Applied
Biosystems,Foster City,CA).
Data Analysis: Genotypes for rs13212041 werecombinedinto twocategories to maintain power.
Peoplehomozygous for themajor allele(A/A) weredistinguished fromthosecarryingatleast one
minor allele(G/_) dueto thelowfrequencyofhomozygous Gindividuals in theparticipant pool
(A/A=508,A/G=277,G/G=33).An ANOVAwas run with adependent variableof BPAQtotal
aggression score,independent predictors ofgender andHTR1Brs13212041 genotype.Fourteen
individuals wereexcluded fromanalysis dueto missing data,leading to afinalparticipant poolof 811.
Observed allelefrequencies for HTR1Brs13212041 (A=0.789 and G=0.211) wereconsistentwith
Caucasian populations (dbSNP,NCBI) andwerewithin Hardy-Weinbergequilibrium, 𝜒2=0.292,
p=0.589.
Is genetic variation in the serotonin 1B receptor associated with aggressive behavior?
Jameson DeFreece, Samuel Jensen, GraceSullivan & Scott F. Stoltenberg
Behavior Genetics Laboratory, Centerfor Brain, Biology & Behavior, Psychology Department
Introduction
• The hypothesized effect of rs13212041 genotype was not found.
• There was a significant difference in mean aggression scores between
males andfemales with males reporting higher levels of aggression
than females.
• The gender differences in the total score of the BPAQ provide support
for gender differences in aggression in previous literature (Eagly &
Steffen 1986; Bohart & Terrall, 2014).
• While some literature suggests that having a G allele lowers the level of
aggression as measured by a set of questions derived from the
Diagnostic and Statistical Manual of Mental Disorders (DSM; Jensen
et al., 2009), we found no effect of this genotype using the BPAQ. This
may be attributed to the DSM’s focus on anger andhostility rather
than the general aggression indicated by the BPAQ.
• This study utilized a large sample size of 825 undergraduate students,
which yields statistical power, giving our results validity.
• Homogeneity of race further benefits the study by predominately
having a Caucasian population (87.4%), limiting the genetic variation
which is beneficial for genetic analysis.
• Considering the higher aggression in males, further research focused
on the mechanisms explaining the gender difference may help identify
ways to reduce aggression.
• Future studies in this area could examine the relationship between this
genotype and specific types of aggression. While rs13212041 genotype
is not related with general aggression as measured by the BPAQ, it is
possible that specific types or aspects of aggression may be related to
this genotype.
• It is also necessary to look beyond Mendelian genetics where one gene
gives rise to one disease. Future studies should incorporate multiple
loci in a genome-wide association study to better understand the
genetic basis of aggression as a whole. Connerand colleagues have
found a relationship with multiple loci of HTR1B, however further
research is needed.
Berma n, M. E., McCloskey, M. S., Fa nning , J. R., Schumacher, J. A., & Cocca ro, E. F. (2009). Serotonin Aug menta tionReduces Response to
Atta ck in Ag g ressive Individua ls. Psycholog ica l Science (Wiley-Bla ckwell), 20(6), 7 14-7 20. doi:10.1111/j.1467 -9280.2009.02355.x
Borha rt, H., & Terrell, H. (2014). Perceptions of Ag g ression a re Colored by Gender Roles. Psycholog ica l Record, 64(3), 441-445.
doi:10.1007 /s407 32-014-0048-5
Buss, A., & Perry, M. (1992). The Ag g ression Questionna ire. Journa l of Persona lity a nd Socia l Psycholog y, 63(2), 452-459.
Conner, T. S., Jensen, K. P., Tennen, H., Furnea ux , H. M., Kra nzler, H. R., & Cova ult, J. (2009). Functiona l polymorphisms in the serotonin 1B
receptor g ene (HTR1B) predict self-reported a ng er a nd hostility a mong young men. Am. J.Med. Genet. America n Journa l of Medica l
Genetics Pa rt B: Neuropsychia tric Genetics, 9999B.
Centers for Disea se Control a nd Prevention (CDC), (2003). Costs of intima te pa rtner violence a g a inst women in the United Sta tes. Atla nta (GA):
CDC, Na tiona l Center for Injury Prevention a nd Control.
Díez, S. U., Escutia , C. V., Pa checo, B. N., Ma rtinez, M. S., Ca ra cena , N. V., & Contrera s, A. O. (2009). Preva lence of intima te pa rtner violence
a nd its rela tionship to physica l a nd psycholog ica l hea lth indica tors. Interna tiona l Journa l ofClinica l Hea lth a nd Psycholog y, 9(3), 411-427.
Ea g ly, A., & Steffen, V., (1986). Gender a nd Ag g ressive Beha vior: A Meta -Ana lytic Review of the Socia l Psycholog ica l Litera ture. Psycholog ica l
Bulletin. Vol. 100, No. 3, 309-330.
Ha nnon, J., & Hoyer, D. (2008). Molecula r biolog y of 5-HT receptors. Serotonin a nd Sleep: Molecula r, Functiona l; a nd Clinica l Aspects, 155-182.
Jensen, K. P., Cova ult, J., Conner, T. S., Tennen, H., Kra nzler, H. R., & Furnea ux , H. M. (2009). A common polymorphism in serotonin receptor
1B mRNA modera tes reg ula tion by miR-96 a nd a ssocia tes with a g g ressive huma n beha viors. Molecula r Psychia try, 14(4), 381-389.
doi:10.1038/mp.2008.15
Kelsoe, J. R. (2010). Beha vioura l neuroscience: A g ene for impulsivity. Na ture, 468(7 327 ), 1049-1050.
N. V., & Contrera s, A. O. (2009). Preva lence of intima te pa rtner violence a nd its rela tionship to physica l a nd psycholog ica l hea lth indica tors.
Interna tiona l Journa l Of Clinica l Hea lth & Psycholog y, 9(3), 411-427 .
Nemeth, N., Kova cs-Na g y, R., Szekely, A., Sa sva ri-Szekely, M., Rona i, Z. (2013). Associa tion of impulsivity a nd polymorphic microRNA-641
ta rg et sites in the SNAP-25 g ene. PLOS., 8(12), doi: 10.137 1/journa l.pone.0084207
Sa udou F, Ama ra DA, Dierich A, LeMeur M, Ra mboz S, Seg u L, Buhot MC, Hen R (1994) Enha nced a g g ressive beha vior in mice la cking 5-HT1B
receptor. Science 265:187 5–187 8
Ta lerico, Eva ns, & Strumpf, 2002). Ta lerico, K. A., Eva ns, L. K., & Strumpf, N. E. (2002). Menta l Hea lth Correla tes of Ag g ression in Nursing
Home Residents With Dementia .Gerontolog ist, 42(2), 169.
Webster, G. D., DeWa ll, C. N., Pond, R. S., Deckma n, T., Jonason, P. K.,Le, B. M., & ... Ba tor, R. J. (2014). The brief a g gression questionna ire:
psychometric a nd beha viora l evidence for a n efficient mea sure of tra it a g g ression. Ag g ressive Beha vior, 40(2), 120-139.
doi:10.1002/a b.21507
This work was partiallyfunded bytheUniversityofNebraskaOfficeof Research andEconomic
Development and thePsychologyDepartment.
Visit theBGL websitefor moreinformation: http://psychology.unl.edu/bgl
• Aggressive behavior leads to a multitude of problems for society. The
monetary cost of Intimate Partner Violence alone is in the billions of
dollars (CDC, 2003).
• In addition to the high monetary cost, aggression has severe
consequences for victims of abuse who are at a higher risk for alcohol
intake anddepression (Díez et al., 2009).
• Males tend to display higher level of aggression than females (Eagly &
Steffen, 1986).
• High levels of serotonin are shown to reduce aggressive behavior
(Berman, McCloskey, Fanning, Schumacher, & Coccaro, 2009).
• The 5-HTR1B gene codes for the 5-HTR1B receptors located on both the
presynaptic andpostsynaptic neuron, which facilitate transmission of
serotonin (Hannon and Hoyer, 2008).
• Mice lacking 5-HTR1B receptors display increasedaggressive behavior
(Saudou et al. 1994).
• HTR1B rs13212041 is a functional single nucleotide polymorphism in the
serotonin 1B receptor gene. Individuals with the G allele have more
serotonin 1B receptors than those with the A allele (Jensen et al., 2009).
• Individuals homozygous for the A allele report a history of more
aggression-like behaviors (starting fires, damaging property, and
fighting) than G-allele carriers (Jensen et al., 2009).
• We hypothesize that males will have a higher mean score on the Buss
Perry Aggression questionnaire (BPAQ) when compared to females.
Furthermore, we hypothesize that carriers of the G allele of rs13212041
will have lower scores of aggression according to the BPAQ.
Methods
Results Conclusions
Literature Cited
Acknowledgements
For more information
Figure 2:BPAQ total aggression score frequency distribution (M=69.18,
SD=1.52, N=6.47).
Figure 1. The5-HTR1B
receptor (purple) is
encoded bythe5-HTR1B
gene.Individuals carrying
theG alleleof rs13212041
haveincreased 1Breceptors
on presynaptic(red) and
postsynaptic(blue)
neurons,whereas carriers
of theAallelehavefewer,
therebyinfluencing
serotonin transmission in
thesynapse(Jensen et al.,
2009).Imagemodified
fromJohn Kelsoe(2010).
Figure 3: Mean BPAQ sum score. Error bars indicate standard error of
male and female groups, showing that males having a significantly higher
mean score than females (p < 0.001).
Figure 4: BPAQ scores for rs13212041 SNP genotype by gender. The effect
of genotype on BPAQ scores is not significant (p = 0.299). There is no
interaction between gender and genotype (p = 0.854).

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Defreece-Jensen-4-14-16

  • 1. Participants:Atotalof 825 undergraduates (70.08% females; 29.22%males; mean age= 20.43yo; 87.4% Caucasian,12.6%other) fromaMidwesternUniversitywererecruited fromthePsychology Department's subject pool.Participants earnedcoursecredit for anhour ofparticipationthat involved completing self-report questionnaires and donating abuccalcellsamplefor genotyping.The University’s InstitutionalReview Boardapproved this studyand allparticipants gavewritten informed consent. Measures:TheBuss-PerryAggression Questionnaire(BPAQ)was usedto assess thelevels of aggression byexamining four types:physicalaggression(“I havethreatenedpeopleI know.”),verbal aggression (“I oftenfind myself disagreeing withpeople”),anger (“Ihavetroublecontrolling my temper.”),and hostility(“I wonder whysometimes I feelso bitter aboutthings.”).Participants responded based on a seven-pointcontinuum(1=extremelyuncharacteristicof meto7=extremely characteristicof me). Atotalscorewas obtained bysummingscores fromallitems (Buss & Perry, 1992). Genotyping: DNAwas extractedfrombuccalcells using theGentraPURGENECellKit (Qiagen, Corp,Valencia,CA).HTR1Brs13212041 was genotyped usingTaqman SNP GenotypingAssays following standard manufacturer protocols (Applied Biosystems,Foster City,CA) in 5uL offinal solution volume.Genotypes weredetermined usingtheStepOnePlus Real-TimePCR Systemand endpoint FAM and VIC fluorescentlevels using AB1 SequenceDetection SoftwareV1.2.3.(Applied Biosystems,Foster City,CA). Data Analysis: Genotypes for rs13212041 werecombinedinto twocategories to maintain power. Peoplehomozygous for themajor allele(A/A) weredistinguished fromthosecarryingatleast one minor allele(G/_) dueto thelowfrequencyofhomozygous Gindividuals in theparticipant pool (A/A=508,A/G=277,G/G=33).An ANOVAwas run with adependent variableof BPAQtotal aggression score,independent predictors ofgender andHTR1Brs13212041 genotype.Fourteen individuals wereexcluded fromanalysis dueto missing data,leading to afinalparticipant poolof 811. Observed allelefrequencies for HTR1Brs13212041 (A=0.789 and G=0.211) wereconsistentwith Caucasian populations (dbSNP,NCBI) andwerewithin Hardy-Weinbergequilibrium, 𝜒2=0.292, p=0.589. Is genetic variation in the serotonin 1B receptor associated with aggressive behavior? Jameson DeFreece, Samuel Jensen, GraceSullivan & Scott F. Stoltenberg Behavior Genetics Laboratory, Centerfor Brain, Biology & Behavior, Psychology Department Introduction • The hypothesized effect of rs13212041 genotype was not found. • There was a significant difference in mean aggression scores between males andfemales with males reporting higher levels of aggression than females. • The gender differences in the total score of the BPAQ provide support for gender differences in aggression in previous literature (Eagly & Steffen 1986; Bohart & Terrall, 2014). • While some literature suggests that having a G allele lowers the level of aggression as measured by a set of questions derived from the Diagnostic and Statistical Manual of Mental Disorders (DSM; Jensen et al., 2009), we found no effect of this genotype using the BPAQ. This may be attributed to the DSM’s focus on anger andhostility rather than the general aggression indicated by the BPAQ. • This study utilized a large sample size of 825 undergraduate students, which yields statistical power, giving our results validity. • Homogeneity of race further benefits the study by predominately having a Caucasian population (87.4%), limiting the genetic variation which is beneficial for genetic analysis. • Considering the higher aggression in males, further research focused on the mechanisms explaining the gender difference may help identify ways to reduce aggression. • Future studies in this area could examine the relationship between this genotype and specific types of aggression. While rs13212041 genotype is not related with general aggression as measured by the BPAQ, it is possible that specific types or aspects of aggression may be related to this genotype. • It is also necessary to look beyond Mendelian genetics where one gene gives rise to one disease. Future studies should incorporate multiple loci in a genome-wide association study to better understand the genetic basis of aggression as a whole. Connerand colleagues have found a relationship with multiple loci of HTR1B, however further research is needed. Berma n, M. E., McCloskey, M. S., Fa nning , J. R., Schumacher, J. A., & Cocca ro, E. F. (2009). Serotonin Aug menta tionReduces Response to Atta ck in Ag g ressive Individua ls. Psycholog ica l Science (Wiley-Bla ckwell), 20(6), 7 14-7 20. doi:10.1111/j.1467 -9280.2009.02355.x Borha rt, H., & Terrell, H. (2014). Perceptions of Ag g ression a re Colored by Gender Roles. Psycholog ica l Record, 64(3), 441-445. doi:10.1007 /s407 32-014-0048-5 Buss, A., & Perry, M. (1992). The Ag g ression Questionna ire. Journa l of Persona lity a nd Socia l Psycholog y, 63(2), 452-459. Conner, T. S., Jensen, K. P., Tennen, H., Furnea ux , H. M., Kra nzler, H. R., & Cova ult, J. (2009). Functiona l polymorphisms in the serotonin 1B receptor g ene (HTR1B) predict self-reported a ng er a nd hostility a mong young men. Am. J.Med. Genet. America n Journa l of Medica l Genetics Pa rt B: Neuropsychia tric Genetics, 9999B. Centers for Disea se Control a nd Prevention (CDC), (2003). Costs of intima te pa rtner violence a g a inst women in the United Sta tes. Atla nta (GA): CDC, Na tiona l Center for Injury Prevention a nd Control. Díez, S. U., Escutia , C. V., Pa checo, B. N., Ma rtinez, M. S., Ca ra cena , N. V., & Contrera s, A. O. (2009). Preva lence of intima te pa rtner violence a nd its rela tionship to physica l a nd psycholog ica l hea lth indica tors. Interna tiona l Journa l ofClinica l Hea lth a nd Psycholog y, 9(3), 411-427. Ea g ly, A., & Steffen, V., (1986). Gender a nd Ag g ressive Beha vior: A Meta -Ana lytic Review of the Socia l Psycholog ica l Litera ture. Psycholog ica l Bulletin. Vol. 100, No. 3, 309-330. Ha nnon, J., & Hoyer, D. (2008). Molecula r biolog y of 5-HT receptors. Serotonin a nd Sleep: Molecula r, Functiona l; a nd Clinica l Aspects, 155-182. Jensen, K. P., Cova ult, J., Conner, T. S., Tennen, H., Kra nzler, H. R., & Furnea ux , H. M. (2009). A common polymorphism in serotonin receptor 1B mRNA modera tes reg ula tion by miR-96 a nd a ssocia tes with a g g ressive huma n beha viors. Molecula r Psychia try, 14(4), 381-389. doi:10.1038/mp.2008.15 Kelsoe, J. R. (2010). Beha vioura l neuroscience: A g ene for impulsivity. Na ture, 468(7 327 ), 1049-1050. N. V., & Contrera s, A. O. (2009). Preva lence of intima te pa rtner violence a nd its rela tionship to physica l a nd psycholog ica l hea lth indica tors. Interna tiona l Journa l Of Clinica l Hea lth & Psycholog y, 9(3), 411-427 . Nemeth, N., Kova cs-Na g y, R., Szekely, A., Sa sva ri-Szekely, M., Rona i, Z. (2013). Associa tion of impulsivity a nd polymorphic microRNA-641 ta rg et sites in the SNAP-25 g ene. 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Visit theBGL websitefor moreinformation: http://psychology.unl.edu/bgl • Aggressive behavior leads to a multitude of problems for society. The monetary cost of Intimate Partner Violence alone is in the billions of dollars (CDC, 2003). • In addition to the high monetary cost, aggression has severe consequences for victims of abuse who are at a higher risk for alcohol intake anddepression (Díez et al., 2009). • Males tend to display higher level of aggression than females (Eagly & Steffen, 1986). • High levels of serotonin are shown to reduce aggressive behavior (Berman, McCloskey, Fanning, Schumacher, & Coccaro, 2009). • The 5-HTR1B gene codes for the 5-HTR1B receptors located on both the presynaptic andpostsynaptic neuron, which facilitate transmission of serotonin (Hannon and Hoyer, 2008). • Mice lacking 5-HTR1B receptors display increasedaggressive behavior (Saudou et al. 1994). • HTR1B rs13212041 is a functional single nucleotide polymorphism in the serotonin 1B receptor gene. Individuals with the G allele have more serotonin 1B receptors than those with the A allele (Jensen et al., 2009). • Individuals homozygous for the A allele report a history of more aggression-like behaviors (starting fires, damaging property, and fighting) than G-allele carriers (Jensen et al., 2009). • We hypothesize that males will have a higher mean score on the Buss Perry Aggression questionnaire (BPAQ) when compared to females. Furthermore, we hypothesize that carriers of the G allele of rs13212041 will have lower scores of aggression according to the BPAQ. Methods Results Conclusions Literature Cited Acknowledgements For more information Figure 2:BPAQ total aggression score frequency distribution (M=69.18, SD=1.52, N=6.47). Figure 1. The5-HTR1B receptor (purple) is encoded bythe5-HTR1B gene.Individuals carrying theG alleleof rs13212041 haveincreased 1Breceptors on presynaptic(red) and postsynaptic(blue) neurons,whereas carriers of theAallelehavefewer, therebyinfluencing serotonin transmission in thesynapse(Jensen et al., 2009).Imagemodified fromJohn Kelsoe(2010). Figure 3: Mean BPAQ sum score. Error bars indicate standard error of male and female groups, showing that males having a significantly higher mean score than females (p < 0.001). Figure 4: BPAQ scores for rs13212041 SNP genotype by gender. The effect of genotype on BPAQ scores is not significant (p = 0.299). There is no interaction between gender and genotype (p = 0.854).