A genome-wide association study of behavioral disinhibition.
paper
Cited
Public
- Authors
- McGue, Matt; Zhang, Yiwei; Miller, Michael B; Basu, Saonli; Vrieze, Scott; Hicks, Brian; Malone, Steve; Oetting, William S; Iacono, William G
- Year
- 2013
- Journal
- Behavior genetics
- PMID
- 23942779
- DOI
- 10.1007/s10519-013-9606-x
- PMCID
- PMC3886341
We report results from a genome wide association study (GWAS) of five quantitative indicators of behavioral disinhibition: nicotine, alcohol consumption, alcohol dependence, illicit drugs, and non-substance related behavioral disinhibition. The sample, consisting of 7,188 Caucasian individuals clustered in 2,300 nuclear families, was genotyped on over 520,000 SNP markers from Illumina's Human 660W-Quad Array. Analysis of individual SNP associations revealed only one marker-component phenotype association, between rs1868152 and illicit drugs, with a p value below the standard genome-wide threshold of 5 × 10(-8). Because we had analyzed five separate phenotypes, we do not consider this single association to be significant. However, we report 13 SNPs that were associated at p < 10(-5) for one phenotype and p < 10(-3) for at least two other phenotypes, which are potential candidates for future investigations of variants associated with general behavioral disinhibition. Biometric analysis of the twin and family data yielded estimates of additive heritability for the component phenotypes ranging from 49 to 70%, GCTA estimates of heritability for the same phenotypes ranged from 8 to 37%. Consequently, even though the common variants genotyped on the GWAS array appear in aggregate to account for a sizable proportion of heritable effects in multiple indicators of behavioral disinhibition, our data suggest that most of the additive heritability remains "missing".
GCTA estimate of the proportion of variance in the Alcohol Consumption factor accounted for by additive genetic effects as a function of the coefficient of genetic relatedness (GRM) threshold. Error bars demarcate plus/minus two standard errors from the estimates. The solid line gives the sample size upon which the corresponding GCTA estimate is based. When the GRM threshold hits .50, first-degree relative pairs are included in the analysis, and when it hits 1.0, monozygotic twin pairs are also included. The standard GCTA estimate is based on a GRM threshold of .025, which is highlighted in blue in the plot.
1–20 of 29
Next →
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Genetic modifiers of frequent vaso-occlusive hospitalizations among individuals with sickle cell disease (SCD). | Ozahata MC et al. | — | 2025 | → |
| Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior. | Lynch WB et al. | — | 2025 | → |
| Variability of transposable elements in six genetic isolates from North-Eastern Italy and their relationship with alcohol consumption, tobacco use and BMI. | Modenini G et al. | — | 2025 | → |
| A genome-wide association study of Chinese and English language phenotypes in Hong Kong Chinese children. | Lin YP et al. | — | 2024 | → |
| Developmental genetic effects on externalizing behavior and alcohol use: Examination across two longitudinal samples. | Elam KK et al. | — | 2024 | → |
| Role of Transposable Elements in behavioral traits: insights from six genetic isolates from North-Eastern Italy | Modenini G et al. | — | 2024 | — |
| An Efficient Bayesian Method for Estimating the Degree of the Skewness of X Chromosome Inactivation Based on the Mixture of General Pedigrees and Unrelated Females. | Kong YF et al. | — | 2023 | → |
| Cross-Sectional Gene-Smoking Interaction Analysis in Relation to Subclinical Atherosclerosis-Results From the IMPROVE Study. | Maitusong B et al. | — | 2023 | → |
| Extensive genetic admixture between Tai-Kadai-speaking people and their neighbours in the northeastern region of the Yungui Plateau inferred from genome-wide variations. | Wang J et al. | — | 2023 | → |
| Genetics and epigenetics of human aggression. | Odintsova VV et al. | — | 2023 | → |
| Mechanisms of cognitive disinhibition explain individual differences in adult attention deficit hyperactivity disorder traits. | Tiego J et al. | — | 2023 | → |
| Personality and peer groups in adolescence: Reciprocal associations and shared genetic and environmental influences. | Clark DA et al. | — | 2023 | → |
| Simultaneous selection of multiple important single nucleotide polymorphisms in familial genome wide association studies data. | Majumdar S et al. | — | 2023 | → |
| Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood. | Deak JD et al. | — | 2022 | → |
| A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase. | Kakhkharova ZI et al. | — | 2022 | → |
| Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies. | Chang XW et al. | — | 2022 | → |
| Detection of Parent-of-Origin Effects for the Variants Associated With Behavioral Disinhibition in the MCTFR Data. | Kong YF et al. | — | 2022 | → |
| Gene-Based Methods for Estimating the Degree of the Skewness of X Chromosome Inactivation. | Li MK et al. | — | 2022 | → |
| Molecular genetics of cocaine use disorders in humans. | Fernàndez-Castillo N et al. | — | 2022 | → |
| Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward. | Beierle JA et al. | — | 2022 | → |
| Adolescent Sexual Development and Peer Groups: Reciprocal Associations and Shared Genetic and Environmental Influences. | Clark DA et al. | — | 2021 | → |
| An Introduction to the Special Issue: Developmental Behavior Genetics and Externalizing Psychopathology. | Elam KK et al. | — | 2021 | → |
| A statistical measure for the skewness of X chromosome inactivation for quantitative traits and its application to the MCTFR data. | Li BH et al. | — | 2021 | → |
| Co-development of alcohol use problems and antisocial peer affiliation from ages 11 to 34: selection, socialization and genetic and environmental influences. | Brislin SJ et al. | — | 2021 | → |
| Genetic underpinnings of affective temperaments: a pilot GWAS investigation identifies a new genome-wide significant SNP for anxious temperament in ADGRB3 gene. | Gonda X et al. | — | 2021 | → |
| Model-based assessment of replicability for genome-wide association meta-analysis. | McGuire D et al. | — | 2021 | → |
| Polygenic Risk for Aggression Predicts Adult Substance Use Disorder Diagnoses via Substance Use Offending in Emerging Adulthood and is Moderated by a Family-Centered Intervention. | Elam KK et al. | — | 2021 | → |
| The influence of regression models on genome-wide association studies of alcohol dependence: a comparison of binary and quantitative analyses. | Li W et al. | — | 2021 | → |
| A Family-Based Genome Wide Association Study of Externalizing Behaviors. | Barr PB et al. | — | 2020 | → |
| A robust and unified framework for estimating heritability in twin studies using generalized estimating equations. | Arbet J et al. | — | 2020 | → |
| Heritability of overlapping impulsivity and compulsivity dimensional phenotypes. | Tiego J et al. | — | 2020 | → |
| On the path towards personalized medicine: Implications of pharmacogenetic studies of alcohol use disorder medications. | Nieto SJ et al. | — | 2020 | → |
| Redefining phenotypes to advance psychiatric genetics: Implications from hierarchical taxonomy of psychopathology. | Waszczuk MA et al. | — | 2020 | → |
| Sexual Development in Adolescence: An Examination of Genetic and Environmental Influences. | Clark DA et al. | — | 2020 | → |
| A case-control genome wide association study of substance use disorder (SUD) identifies novel variants on chromosome 7p14.1 in patients from the United Arab Emirates (UAE). | Alblooshi H et al. | — | 2019 | → |
| A Hierarchical Taxonomy of Psychopathology Can Transform Mental Health Research. | Conway CC et al. | — | 2019 | → |
| Conduct disorder. | Fairchild G et al. | — | 2019 | → |
| Fine-mapping scan of bipolar disorder susceptibility loci in Latino pedigrees. | Gonzalez S et al. | — | 2019 | → |
| Genetic determinants of beverage consumption: Implications for nutrition and health. | Cornelis MC | — | 2019 | → |
| Genetic loci for alcohol-related life events and substance-induced affective symptoms: indexing the "dark side" of addiction. | Peng Q et al. | — | 2019 | → |
| Genetic variation in health insurance coverage. | Wehby GL et al. | — | 2019 | → |
| Genomics of human aggression: current state of genome-wide studies and an automated systematic review tool. | Odintsova VV et al. | — | 2019 | → |
| A linear mixed model framework for gene-based gene-environment interaction tests in twin studies. | Coombes BJ et al. | — | 2018 | → |
| Evaluation of previous substance dependence genome-wide significant findings in a Spanish sample. | Pineda-Cirera L et al. | — | 2018 | → |
| GABA<sub>A</sub> receptor polymorphisms in alcohol use disorder in the GWAS era. | Koulentaki M et al. | — | 2018 | → |
| Human Genetics of Addiction: New Insights and Future Directions. | Hancock DB et al. | — | 2018 | → |
| Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. | Huckins LM et al. | — | 2018 | → |
| Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries. | Feitosa MF et al. | — | 2018 | → |
| The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design. | Iacono WG et al. | — | 2018 | → |
| A combination test for detection of gene-environment interaction in cohort studies. | Coombes B et al. | — | 2017 | → |
| Exploring genetic associations with ceRNA regulation in the human genome. | Li MJ et al. | — | 2017 | → |
| Identifying pleiotropic genes in genome-wide association studies from related subjects using the linear mixed model and Fisher combination function. | Yang JJ et al. | — | 2017 | → |
| Phenotypic and Genetic Relationship Between BMI and Drinking in a Sample of UK Adults. | Wills AG et al. | — | 2017 | → |
| Resampling-based tests for Lasso in genome-wide association studies. | Arbet J et al. | — | 2017 | → |
| Revealing phenotype-associated functional differences by genome-wide scan of ancient haplotype blocks. | Onuki R et al. | — | 2017 | → |
| Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders. | Cho SB et al. | — | 2017 | → |
| A genome-wide approach to children's aggressive behavior: The EAGLE consortium. | Pappa I et al. | — | 2016 | → |
| A genome-wide investigation of food addiction. | Cornelis MC et al. | — | 2016 | → |
| An efficient genome-wide association test for multivariate phenotypes based on the Fisher combination function. | Yang JJ et al. | — | 2016 | → |
| A Review of Genome-Wide Association Studies of Stimulant and Opioid Use Disorders. | Jensen KP | — | 2016 | → |
| A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Five Longitudinal Studies. | Samek DR et al. | — | 2016 | → |
| Commentary on Verweij et al. (2016): Conduct problems and substance use-genetic and environmental perspectives on sex differences. | Few LR et al. | — | 2016 | → |
| Genetic influences on adolescent behavior. | Dick DM et al. | — | 2016 | → |
| Molecular genetic approaches to understanding the comorbidity of psychiatric disorders. | Gizer IR | — | 2016 | → |
| Predicting substance use in emerging adulthood: A genetically informed study of developmental transactions between impulsivity and family conflict. | Elam KK et al. | — | 2016 | → |
| Single nucleotide polymorphisms in the REG-CTNNA2 region of chromosome 2 and NEIL3 associated with impulsivity in a Native American sample. | Ehlers CL et al. | — | 2016 | → |
| Top 10 Replicated Findings From Behavioral Genetics. | Plomin R et al. | — | 2016 | → |
| Alcohol Dependence Genetics: Lessons Learned From Genome-Wide Association Studies (GWAS) and Post-GWAS Analyses. | Hart AB et al. | — | 2015 | → |
| Altered CSMD1 Expression Alters Cocaine-Conditioned Place Preference: Mutual Support for a Complex Locus from Human and Mouse Models. | Drgonova J et al. | — | 2015 | → |
| Association of substance dependence phenotypes in the COGA sample. | Wetherill L et al. | — | 2015 | → |
| Genome-wide association data suggest ABCB1 and immune-related gene sets may be involved in adult antisocial behavior. | Salvatore JE et al. | — | 2015 | → |
| Genome-Wide Association Study of Behavioral Disinhibition in a Selected Adolescent Sample. | Derringer J et al. | — | 2015 | → |
| Genomic influences on alcohol problems in a population-based sample of young adults. | Edwards AC et al. | — | 2015 | → |
| Risky Business: Pathways to Progress in Biologically Informed Studies of Psychopathology. | Agrawal A et al. | — | 2015 | → |
| Shared additive genetic influences on DSM-IV criteria for alcohol dependence in subjects of European ancestry. | Palmer RH et al. | — | 2015 | → |
| The role of conduct disorder in the relationship between alcohol, nicotine and cannabis use disorders. | Grant JD et al. | — | 2015 | → |
| Genetic, psychosocial, and demographic factors associated with social disinhibition in Mexican-origin youth. | Archer NP et al. | — | 2014 | → |
| Genome-wide scans of genetic variants for psychophysiological endophenotypes: a methodological overview. | Iacono WG et al. | — | 2014 | → |
| Genotype-environment correlation in the era of DNA. | Plomin R | — | 2014 | → |
| Heritability and molecular-genetic basis of resting EEG activity: a genome-wide association study. | Malone SM et al. | — | 2014 | → |
| Heritability and molecular-genetic basis of the P3 event-related brain potential: a genome-wide association study. | Malone SM et al. | — | 2014 | → |
| In search of rare variants: preliminary results from whole genome sequencing of 1,325 individuals with psychophysiological endophenotypes. | Vrieze SI et al. | — | 2014 | → |
| Knowns and unknowns for psychophysiological endophenotypes: integration and response to commentaries. | Iacono WG et al. | — | 2014 | → |
| Rare nonsynonymous exonic variants in addiction and behavioral disinhibition. | Vrieze SI et al. | — | 2014 | → |
| The adolescent origins of substance use disorders: a behavioral genetic perspective. | McGue M et al. | — | 2014 | → |
| The Genetics, Neurogenetics and Pharmacogenetics of Addiction. | Demers CH et al. | — | 2014 | → |
| A rapid gene-based genome-wide association test with multivariate traits. | Basu S et al. | — | 2013 | → |
| Three mutually informative ways to understand the genetic relationships among behavioral disinhibition, alcohol use, drug use, nicotine use/dependence, and their co-occurrence: twin biometry, GCTA, and genome-wide scoring. | Vrieze SI et al. | — | 2013 | → |