Examining associations between genetic and neural risk for externalizing behaviors in adolescence and early adulthood.
- Authors
- Brislin, Sarah J; Salvatore, Jessica E; Meyers, Jacquelyn M; Kamarajan, Chella; Plawecki, Martin H; Edenberg, Howard J; Kuperman, Samuel; Tischfield, Jay; Hesselbrock, Victor; Anokhin, Andrey P; Chorlian, David B; Schuckit, Marc A; Nurnberger, John I; Bauer, Lance; Pandey, Gayathri; Pandey, Ashwini K; Kramer, John R; Chan, Grace; Porjesz, Bernice; COGA Collaborators; Dick, Danielle M
- Year
- 2024
- Journal
- Psychological medicine
- PMID
- 37203444
- DOI
- 10.1017/S0033291723001174
- PMCID
- PMC11010461
BACKGROUND: Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic liability is conferred in part through associations with more proximal neurophysiological risk markers. METHODS: Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic scores for externalizing (EXT PGS) were calculated. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol and cannabis use, and antisocial behavior) were assessed in participants of European (EA; = 2851) and African ancestry (AA; = 1402). Analyses were also stratified by age (adolescents, age 12-17 and young adults, age 18-32). RESULTS: The EXT PGS was significantly associated with higher levels of externalizing behaviors among EA adolescents and young adults as well as AA young adults. P3 was inversely associated with externalizing behaviors among EA young adults. EXT PGS was not significantly associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PGS and externalizing behaviors. CONCLUSIONS: Both the EXT PGS and P3 amplitude were significantly associated with externalizing behaviors among EA young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing.
Associations among study variables. (a) Associations with externalizing behavior score among EA individuals. Ξ² are standardized beta weights from separate linear regression models for EXT polygenic score (PGS) and Visual oddball P3 amplitude (P3). (b) Associations with externalizing behavior score among AA individuals. (c) Association between P3 amplitude and EXT PGS scores for European (EA) and African (AA) ancestry individuals. Ξ² are standardized beta weights from separate linear regression models for EXT PGS and Visual oddball P3 amplitude (P3).
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| Citation | PMID | DOI | Status |
|---|---|---|---|
| American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders: DSM-5β’ (5th ed., pp. xliv, 947). Arlington, VA, US: American Psychiatric Publishing, Inc. 10.1176/appi.books.9780890425596. | β | β | β |
| BaurleyJW, EdlundCK, PardameanCI, ContiDV, & BergenAW (2016). Smokescreen: a targeted genotyping array for addiction research. BMC Genomics, 17(1), 1β12.26921259 10.1186/s12864-016-2495-7PMC4769529 | β | β | β |
| BegleiterH, ReichT, HesselbrockV, PorjeszB, LiTK, SchuckitMA, β¦ RiceJP (1995). The collaborative study on the genetics of alcoholism. Alcohol Health and Research World, 19, 228β236.31798102 PMC6875768 | β | β | β |
| BucholzKK, CadoretR, CloningerCR, DinwiddieSH, HesselbrockVM, NurnbergerJI, β¦ SchuckitMA (1994). A new, semi-structured psychiatric interview for use in genetic linkage studies: A report on the reliability of the SSAGA. Journal of Studies on Alcohol, 55(2), 149β158. https://doi.org/10/gn6gww.8189735 10.15288/jsa.1994.55.149 | β | β | β |
| CohenHL, WangW, PorjeszB, BauerL, KupermanS, OβConnorSJ, β¦ BegleiterH (1994). Visual P300: an interlaboratory consistency study. Alcohol, 11(6), 583β587.7865162 10.1016/0741-8329(94)90087-6 | β | β | β |
| DickDM, VikenRJ, KaprioJ, PulkkinenL, & RoseRJ (2005). Understanding the covariation among childhood externalizing symptoms: Genetic and environmental influences on conduct disorder, attention deficit hyperactivity disorder, and oppositional defiant disorder symptoms. Journal of Abnormal Child Psychology, 33(2), 219β229. https://doi.org/10/btk6k4.15839499 10.1007/s10802-005-1829-8 | β | β | β |
| DuncanL, ShenH, GelayeB, MeijsenJ, ResslerK, FeldmanM, β¦ DomingueB (2019). Analysis of polygenic risk score usage and performance in diverse human populations. Nature Communications, 10(1), 3328. 10.1038/s41467-019-11112-0.PMC665847131346163 | β | β | β |
| EdenbergHJ (2002). The collaborative study on the genetics of alcoholism: An update. Alcohol Research & Health, 26, 214β218.12875050 PMC6683843 | β | β | β |
| EmeR (2016). Sex differences in the prevalence and expression of externalizing behavior. In BeauchaineTP, & HinshawSP (Eds.), Oxford library of psychology. The Oxford handbook of externalizing spectrum disorders (pp. 239β263). New York, NY, US: Oxford University Press. | β | β | β |
| EuserAS, ArendsLR, EvansBE, Greaves-LordK, HuizinkAC, & FrankenIHA (2012). The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: A meta-analytic investigation. Neuroscience & Biobehavioral Reviews, 36(1), 572β603. 10.1016/j.neubiorev.2011.09.002.21964481 | β | β | β |
| GeT, ChenCY, NiY, FengYCA, & SmollerJW (2019). Polygenic prediction via Bayesian regression and continuous shrinkage priors. Nature Communications, 10(1), 1776.10.1038/s41467-019-09718-5PMC646799830992449 | β | β | β |
| GilmoreCS, MaloneSM, BernatEM, & IaconoWG (2010). Relationship between the P3 event-related potential, its associated time-frequency components, and externalizing psychopathology. Psychophysiology, 47(1), 123β132. 10.1111/j.1469-8986.2009.00876.x.19674392 PMC2860032 | β | β | β |
| GrotzingerAD, RhemtullaM, de VlamingR, RitchieSJ, MallardTT, HillWD, β¦ Tucker-DrobEM (2019). Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits. Nature Human Behaviour, 3(5), 513β525. 10.1038/s41562-019-0566-x.PMC652014630962613 | β | β | β |
| HarperJ, LiuM, MaloneSM, McGueM, IaconoWG, & VriezeSI (2021). Using multivariate endophenotypes to identify psychophysiological mechanisms associated with polygenic scores for substance use, schizophrenia, and education attainment. Psychological Medicine, 52, 1β11. 10.1017/S0033291721000763.PMC844878433731234 | β | β | β |
| HesselbrockM, EastonC, BucholzKK, SchuckitM, & HesselbrockV (1999). A validity study of the SSAGA-a comparison with the SCAN. Addiction, 94(9), 1361β1370.10615721 10.1046/j.1360-0443.1999.94913618.x | β | β | β |
| HicksBM, BernatE, MaloneSM, IaconoWG, PatrickCJ, KruegerRF, & McgueM (2007). Genes mediate the association between P3 amplitude and externalizing disorders. Psychophysiology, 44(1), 98β105.17241145 10.1111/j.1469-8986.2006.00471.xPMC2365473 | β | β | β |
| IaconoWG (2018). Endophenotypes in psychiatric disease: Prospects and challenges. Genome Medicine, 10(1), 11. 10.1186/s13073-018-0526-5.29471866 PMC5824588 | β | β | β |
| IaconoWG, & MaloneSM (2011). Developmental endophenotypes: Indexing genetic risk for substance abuse with the P300 brain event-related potential. Child Development Perspectives, 5(4), 239β247.22247735 10.1111/j.1750-8606.2011.00205.xPMC3254094 | β | β | β |
| IaconoWG, MaloneSM, & McGueM (2003). Substance use disorders, externalizing psychopathology, and P300 event-related potential amplitude. International Journal of Psychophysiology, 48(2), 147β178.12763572 10.1016/s0167-8760(03)00052-7 | β | β | β |
| IaconoWG, MaloneSM, & VriezeSI (2017). Endophenotype best practices. International Journal of Psychophysiology, 111, 115β144. 10.1016/j.ijpsycho.2016.07.516.27473600 PMC5219856 | β | β | β |
| Karlsson LinnΓ©rR, MallardTT, BarrPB, Sanchez-RoigeS, MadoleJW, DriverMN, β¦ DickDM (2021). Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction. Nature Neuroscience, 24(10), 1367β1376. 10.1038/s41593-021-00908-3.34446935 PMC8484054 | β | β | β |
| KatsanisJ, IaconoWG, McgueMK, & CarlsonSR (1997). P300 event-related potential heritability in monozygotic and dizygotic twins. Psychophysiology, 34(1), 47β58.9009808 10.1111/j.1469-8986.1997.tb02415.x | β | β | β |
| KellerMC (2014). GeneΓenvironment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75(1), 18β24. 10.1016/j.biopsych.2013.09.006.24135711 PMC3859520 | β | β | β |
| KotovR, KruegerRF, WatsonD, AchenbachTM, AlthoffRR, BagbyRM, β¦ ZimmermanM (2017). The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies. Journal of Abnormal Psychology, 126(4), 454β477. 10.1037/abn0000258.28333488 | β | β | β |
| KruegerRF, HobbsKA, ConwayCC, DickDM, DretschMN, & EatonNR, β¦ HiTOP Utility Workgroup. (2021). Validity and utility of Hierarchical Taxonomy of Psychopathology (HiTOP): II. Externalizing superspectrum. World Psychiatry, 20(2), 171β193. 10.1002/wps.20844.34002506 PMC8129870 | β | β | β |
| KruegerRF, MarkonKE, PatrickCJ, BenningSD, & KramerMD (2007). Linking antisocial behavior, substance use, and personality: An integrative quantitative model of the adult externalizing spectrum. Journal of Abnormal Psychology, 116(4), 645β666. 10.1037/0021-843X.116.4.645.18020714 PMC2242625 | β | β | β |
| KuoSI-C, SalvatoreJE, BarrPB, AlievF, AnokhinA, & BucholzKK, β¦ Externalizing Consortium. (2021). Mapping pathways by which genetic risk influences adolescent externalizing behavior: The interplay between externalizing polygenic risk scores, parental knowledge, and peer substance use. Behavior Genetics, 51(5), 543β558. 10.1007/s10519-021-10067-7.34117972 PMC8403154 | β | β | β |
| LaiD, WetherillL, BertelsenS, CareyCE, KamarajanC, KapoorM, β¦ ForoudT (2019). Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. Genes, Brain and Behavior, 18(6), e12579. 10.1111/gbb.12579.31090166 PMC6612573 | β | β | β |
| LiC-H (2016). Confirmatory factor analysis with ordinal data: Comparing robust maximum likelihood and diagonally weighted least squares. Behavior Research Methods, 48(3), 936β949. 10.3758/s13428-015-0619-7.26174714 | β | β | β |
| LiuM, MaloneSM, VaidyanathanU, KellerMC, AbecasisG, McGueM, β¦ VriezeSI (2017). Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 47(6), 1116β1125. 10.1017/S0033291716003184.27995817 PMC5352523 | β | β | β |
| MarkonKE, ChmielewskiM, & MillerCJ (2011). The reliability and validity of discrete and continuous measures of psychopathology: A quantitative review. Psychological Bulletin, 137(5), 856β879. APA PsycArticles (2011-09705-001). 10.1037/a0023678.21574681 | β | β | β |
| MuthenLK, & MuthΓ©nBO (1998β2017). Mplus Userβs Guide (8th Edition). Los Angeles, CA: Muthen & Muthen. | β | β | β |
| OβConnorS, MorzoratiS, ChristianJC, & LiTK (1994). Heritable features of the auditory oddball event-related potential: peaks, latencies, morphology and topography. Electroencephalography and Clinical Neurophysiology/Evoked Potentials Section, 92(2), 115β125.10.1016/0168-5597(94)90052-37511509 | β | β | β |
| PatrickCJ, BernatEM, MaloneSM, IaconoWG, KruegerRF, & McGueM (2006). P300 amplitude as an indicator of externalizing in adolescent males. Psychophysiology, 43(1), 84β92. 10.1111/j.1469-8986.2006.00376.x.16629688 PMC2242347 | β | β | β |
| PerkinsER, LatzmanRD, & PatrickCJ (2020). Interfacing neural constructs with the Hierarchical Taxonomy of Psychopathology: βWhyβ and βhowβ. Personality and Mental Health, 14(1), 106β122. 10.1002/pmh.1460.31456351 | β | β | β |
| PorjeszB, & BegleiterH (1998). Genetic basis of event-related potentials and their relationship to alcoholism and alcohol use. Journal of Clinical Neurophysiology, 15(1), 44β57. 10.1097/00004691-199801000-00006.9502512 | β | β | β |
| PorjeszB, RangaswamyM, KamarajanC, JonesKA, PadmanabhapillaiA, & BegleiterH (2005). The utility of neurophysiological markers in the study of alcoholism. Clinical Neurophysiology, 116(5), 993β1018. 10.1016/j.clinph.2004.12.016.15826840 | β | β | β |
| R Core Team. (2021). R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing. Retrieved from https://www.R-project.org/. | β | β | β |
| ReichT, EdenbergHJ, GoateA, WilliamsJT, RiceJP, Van EerdeweghP, β¦ BegleiterH (1998). Genome-wide search for genes affecting the risk for alcohol dependence. American Journal of Medical Genetics, 81(3), 207β215.9603606 | β | β | β |
| ShulmanEP, SmithAR, SilvaK, IcenogleG, DuellN, CheinJ, & SteinbergL (2016). The dual systems model: Review, reappraisal, and reaffirmation. Developmental Cognitive Neuroscience, 17, 103β117. 10.1016/j.dcn.2015.12.010.26774291 PMC6990093 | β | β | β |
| Van BeijsterveldtCE, MolenaarPC, De GeusEJ, & BoomsmaDI (1996). Heritability of human brain functioning as assessed by electroencephalography. American Journal of Human Genetics, 58(3), 562.8644716 PMC1914558 | β | β | β |
| VenablesNC, HicksBM, YanceyJR, KramerMD, NelsonLD, StricklandCM, β¦ PatrickCJ (2017). Evidence of a prominent genetic basis for associations between psychoneurometric traits and common mental disorders. International Journal of Psychophysiology, 115, 4β12. 10.1016/j.ijpsycho.2016.09.011.27671504 PMC5364073 | β | β | β |
| WaldmanID, PooreHE, van HulleC, RathouzPJ, & LaheyBB (2016). External validity of a hierarchical dimensional model of child and adolescent psychopathology: Tests using confirmatory factor analyses and multivariate behavior genetic analyses. Journal of Abnormal Psychology, 125, 1053β1066. 10.1037/abn0000183.27819467 PMC6810679 | β | β | β |
| YoonHH, IaconoWG, MaloneSM, & McgueM (2006). Using the brain P300 response to identify novel phenotypes reflecting genetic vulnerability for adolescent substance misuse. Addictive Behaviors, 31(6), 1067β1087.16644137 10.1016/j.addbeh.2006.03.036 | β | β | β |
| YoungSE, StallingsMC, CorleyRP, KrauterKS, & HewittJK (2000). Genetic and environmental influences on behavioral disinhibition. American Journal of Medical Genetics, 96(5), 684β695. 10.1002/1096-8628(20001009)96:5<684::AID-AJMG16>3.0.CO;2-G.11054778 | β | β | β |
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Characterizing the co-occurrence of alcohol experimentation and suicidal thoughts and behaviors in early adolescence. | Lannoy S et al. | β | 2026 | β |
| Interplay between polygenic risk and family processes in predicting trajectories of adolescent externalizing behaviors. | Su J et al. | β | 2025 | β |
| The collaborative study on the genetics of alcoholism: Brain function. | Meyers JL et al. | β | 2023 | β |