Genetic correlates of the development of theta event related oscillations in adolescents and young adults.
- Authors
- Chorlian, David B; Rangaswamy, Madhavi; Manz, Niklas; Meyers, Jacquelyn L; Kang, Sun J; Kamarajan, Chella; Pandey, Ashwini K; Wang, Jen-Chyong; Wetherill, Leah; Edenberg, Howard; Porjesz, Bernice
- Year
- 2017
- Journal
- International journal of psychophysiology : official journal of the International Organization of Psychophysiology
- PMID
- 27847216
- DOI
- 10.1016/j.ijpsycho.2016.11.007
- PMCID
- PMC5456461
The developmental trajectories of theta band (4-7Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. Associations between the theta EROs and genotypic variants of 4 KCNJ6 single nucleotide polymorphisms (SNPs) were found to vary with age, sex, scalp location, and task modality. Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta EROs in adults in a previous family genome wide association study. Since measures of the P3 response have been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of genetic effects on its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions.
Log-transformed theta ERO total power trajectory means (s(t)) in auditory (left column) and visual (right column) modalities presented in three views: Top row: Development curves: s(t). Middle row: Relative development curves s̃(t) = (s(t) − mean(s(t)))/mean(s(t)). Values are shown as relative to the mean value of the trajectory. Plots of relative values emphasize similarities and differences in overall shape, rather than in values. Bottom row: Rates of change of development curves: ds(t)/dt = (ds(t)/dt)/s(t). Each line in this graph represents the slope of the corresponding line in the graph in the top row at the corresponding age. The y-axis is inverted in order to illustrate the decrease in absolute value of the slopes with time. All line styles and colors of the graphs follow the legends in the middle row.
Intramodal and Intermodal Phenotypic Correlations. Intramodal correlations in top panel: Left Columns: Auditory correlations; Right Columns: Visual Correlations. Intermodal correlations in bottom panel: Left Columns: Matching locations; Right Columns: Non-matching locations. (For non-matching locations the first electrode is the auditory the second the visual.) Note that the scales are different between in the top and bottom panels.
Distribution of observed p-values and a conservative estimate of the distribution of the p-values of the cases in which there were no genotypic associations in the data. There were 6288 observed p-values of which 4000 were estimated to be instances with no genotypic association. The bins are .005 wide. This plot corresponds to figure 1 in Storey and Tibshirani (2003).
KCNJ6 SNPs: Identification of significant associations between KCNJ6 SNPs and theta band ERO trajectories for a coarse age scale (seven overlapping 3 year age ranges) for each sex-modality combination. Each panel contains the information for one sex-modality combination for all 4 SNPs. The sex-modality combination is labeled at the top of each panel. For each SNP the rows are ordered Fz, Cz, Pz from top to bottom and ages increase from left to right. The median p-value for each sex-SNP-phenotype-age combination is −log10 transformed and multiplied by the sign of the effect size of the minor allele for each combination and color coded in the plot. Thresholding at p < .0136 controls the false discovery rate at 5% for the representation of age-specific p values by median p values in each age range. Markers on the color bars on the right of each plot indicate the signed median p-value on a −log10 scale. (−log10(.0136) = 1.87.)
KCNJ6 SNPs: Phenotype-Genotype association trajectories shown by estimates of effect sizes for the minor allele in the additive genetic model in auditory and visual modalities for each SNP. One SNP per row. Males: two left columns; Females: two right columns. The auditory modality is to the left of the visual modality for each sex. Electrodes are color coded: FZ blue, CZ green, PZ red. Thick markers in plotted trajectories and at the bottom edge indicate ages where p < 0.009 for genotypic effects.
Estimate of mean log transformed visual ERO values at the Fz electrode by genotype and sex for each of the KCNJ6 SNPs analyzed. Plot legend indicates values by sex and number of minor alleles.
| # | Section | Preview |
|---|---|---|
| 40 | 2. Methods and Materials — 2.4. Statistical Methodology — 2.4.2. Age variation of genotypic effects — Identification of Significant SNPs | the regression calculations were performed, in the interest of condensation of information and ease… |
| 41 | 2. Methods and Materials — 2.4. Statistical Methodology — 2.4.2. Age variation of genotypic effects — Relation of genotypic values to phenotypic correlations | Given that the phenotypic variables show high degrees of correlation, as shown in Figure 2 and… |
| 42 | 2. Methods and Materials — 2.4. Statistical Methodology — 2.4.2. Age variation of genotypic effects — Relation of genotypic values to phenotypic correlations | Noting the degree of heterogeneity between SNPs apparent in the association trajectories, and the… |
| 43 | 2. Methods and Materials — 2.4. Statistical Methodology — 2.4.2. Age variation of genotypic effects — Relation of genotypic values to phenotypic correlations | between modalities is the sum of number of significant values for the two modalities for each… |
| 44 | 3. Results — 3.1. Phenotypic (ERO) results | Results from a previous study of developmental trajectories of the phenotypes from the dataset used… |
| 45 | 3. Results — 3.1. Phenotypic (ERO) results — 3.1.1. ERO power values | ERO power values had the following characteristics: |
| 46 | 3. Results — 3.1. Phenotypic (ERO) results — 3.1.1. ERO power values | To illustrate the difference between male and female development in the trajectory plots, three… |
| 47 | 3. Results — 3.1. Phenotypic (ERO) results — 3.1.2. ERO power correlations | ERO power correlations had the following characteristics, as can be seen in Figure 2: |
| 48 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association | The trajectories of association were examined by the methods described in section 2.4.2. Most… |
| 49 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | Using the method described in Section 2.4.2, an algorithm adapted from Storey and Tibshirani (2003)… |
| 50 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | Figures 4 and 5 show the results of applying the criteria in the preceding paragraph to the data on… |
| 51 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | On the coarse-grained time scale, the identification of significant associations between KCNJ6 SNPs… |
| 52 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | On the finer-grained time scale, sex-modality specific trajectories of SNP-phenotype association as… |
| 53 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | Effect sizes of genotype range from 0.1 to greater than 0.2 in absolute value when statistically… |
| 54 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | The significance of the genotypic results must be understood in terms of biological processes… |
| 55 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.1. Trajectories of association — Identification of significant SNPs | Since the graphs show cumulative effects, the indications of significant difference at the bottom of… |
| 56 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.2. Correspondence between association trajectories | Visual assessment of correspondences between association trajectories can be made by examination of… |
| 57 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.2. Correspondence between association trajectories | Permutation tests, as described in section 2.4.2 were carried out to determine whether the… |
| 58 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.2. Correspondence between association trajectories — Test of intramodal correspondences | There were 112 correspondence measures for the intramodal data, as defined in section 2.4.2, (7 age… |
| 59 | 3. Results — 3.2. Genetic effects and gene × sex interactions — 3.2.2. Correspondence between association trajectories — Test of intermodal correspondences | There were 162 correspondence measures for the intermodal data, each of which was assigned a value… |
| Name | Type |
|---|---|
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| Acute/chronic medical illnesses affecting brain function | phenotype |
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| ADHD | phenotype |
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| age | phenotype |
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| Alcoholic proband | cohort |
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| auditory evoked potentials local | phenotype |
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| bilateral prefrontal cortex (medial and lateral) local | anatomy |
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| brain tissue | anatomy |
| Carlson and Iacono 2006 study local | cohort |
| central | anatomy |
| Chorlian2015 local | cohort |
| Chorlian et al., 2015 dataset local | cohort |
| Chorlian et al. 2015 study local | cohort |
| CHRM2 | gene |
| coding variant | cohort |
| COGA subjects local | cohort |
| Colantuoni et al., 2011 local | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| community | cohort |
| Community local | phenotype |
| community (comparison) families local | cohort |
| COMT | gene |
| COMT Val158Met | gene |
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| cortical thickness | phenotype |
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| Cousminer et al. 2013 study local | cohort |
| CRHR1 | gene |
| cross-modal phenotypic correlation local | phenotype |
| cross-regional phenotypic correlation local | phenotype |
| current study | cohort |
| CurrentStudy | cohort |
| Cz | anatomy |
| Cz auditory local | phenotype |
| Cz visual local | phenotype |
| developmental trajectory | phenotype |
| development of brain networks local | phenotype |
| epilepsy | phenotype |
| episodic memory | phenotype |
| European ancestry | cohort |
| executive function | phenotype |
| externalizing disorders | phenotype |
| Family type local | phenotype |
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| full sample | cohort |
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| Fz auditory local | phenotype |
| Fz visual local | phenotype |
| general decrease in power local | phenotype |
| genetic ancestry | phenotype |
| genetic variants | cohort |
| genotypic covariates local | variant |
| Global Biological Factor local | phenotype |
| global connectivity local | anatomy |
| gray matter | anatomy |
| gray matter density local | anatomy |
| GRM8 | gene |
| Head injury | phenotype |
| healthy controls | cohort |
| height | phenotype |
| Height velocity local | phenotype |
| hepatic encephalopathy | phenotype |
| Hill et al. (2013) local | cohort |
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| HIV infection | phenotype |
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| Indiana University School of Medicine | cohort |
| individual SNPs | cohort |
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| intercept | phenotype |
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| IQ | phenotype |
| Kang2012_family_GWAS local | cohort |
| Kang et al., 2011 local | cohort |
| Kang et al. 2012 study local | cohort |
| Katsanis et al. 1997 study local | cohort |
| Kcnj6 | gene |
| KCNJ6 SNP local | variant |
| LIN28B | gene |
| Liver cirrhosis | phenotype |
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| MAPK3 | gene |
| Mini Mental State Examination score <25 | phenotype |
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| multiplex alcoholic families local | cohort |
| myelin | phenotype |
| Naumova et al., 2013 local | cohort |
| Neurosurgery | phenotype |
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| oscillatory activity | phenotype |
| P3 amplitude | phenotype |
| P3 component | phenotype |
| P3 electrophysiological measure local | phenotype |
| P3 electrophysiological measures local | phenotype |
| P3 related electrophysiological measures local | phenotype |
| P3 related electrophysiology local | phenotype |
| parietal cortex | anatomy |
| phenotype | phenotype |
| Phenotypic Variable local | phenotype |
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| prepubertal males local | cohort |
| Prospective Study of the Collaborative Study on the Genetics of Alcoholism (COGA) local | cohort |
| Psychoses | phenotype |
| pubertal males local | cohort |
| PXMP3 local | gene |
| Pz | anatomy |
| Pz auditory local | phenotype |
| Pz visual local | phenotype |
| recognition memory | phenotype |
| resting state | phenotype |
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| right inferior frontal gyrus activation local | phenotype |
| right-lateralized frontal region of ventral attention network | anatomy |
| right-lateralized temporoparietal region of ventral attention network | anatomy |
| rs1787422 local | variant |
| rs2070995 local | variant |
| rs2835850 local | variant |
| rs702859 | variant |
| rs857975 local | variant |
| rs858008 local | variant |
| scalp location local | anatomy |
| Scalp location local | anatomy |
| Scalp Location local | anatomy |
| scalp locations local | anatomy |
| schizophrenia | phenotype |
| sensory deficits | phenotype |
| sex | phenotype |
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| slope | phenotype |
| SNP | cohort |
| SNP4 local | variant |
| Stead et al., 2006 local | cohort |
| Structural brain feature local | phenotype |
| subjects | cohort |
| substance abuse | phenotype |
| SUNY Downstate Medical Center | cohort |
| superior parietal cortex | anatomy |
| supra-marginal gyrus local | anatomy |
| Supra-marginal gyrus local | anatomy |
| synaptic pruning | phenotype |
| synonymous SNPs local | variant |
| task-related brain activity | phenotype |
| temporal | anatomy |
| temporal cortex | anatomy |
| Temporoparietal region of ventral attention network local | anatomy |
| theta band ERO trajectories local | phenotype |
| theta band event related oscillation local | phenotype |
| theta band oscillation local | phenotype |
| theta ERO | phenotype |
| theta EROs | phenotype |
| theta ERO values local | phenotype |
| Twin cohort | cohort |
| University of California at San Diego | cohort |
| University of Connecticut Health Center | cohort |
| University of Iowa | cohort |
| van Beijsterveldt et al. 1998 study local | cohort |
| van Beijsterveldt et al. 2001 study local | cohort |
| ventral attention network | anatomy |
| VGLL3 local | gene |
| visual Fz phenotype local | phenotype |
| visual modality | anatomy |
| visual theta ERO power local | phenotype |
| Washington University School of Medicine in St. Louis | cohort |
| white matter | anatomy |
| Widén et al. 2010 study local | cohort |
| working memory | phenotype |
| young adults | cohort |
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In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Upregulated GIRK2 Counteracts Ethanol-Induced Changes in Excitability and Respiration in Human Neurons. | Prytkova I et al. | — | 2024 | → |
| 5. Collaborative Study on the Genetics of Alcoholism: Functional genomics. | Gameiro-Ros I et al. | — | 2023 | → |
| Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. | Popova D et al. | — | 2023 | → |
| Genetic influences vary by age and sex: Trajectories of the association of cholinergic system variants and theta band event related oscillations | Chorlian DB et al. | — | 2023 | — |
| Longitudinal stability and change in time-frequency measures from an oddball task during adolescence and early adulthood. | Malone SM et al. | — | 2023 | → |
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| A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior. | Meyers JL et al. | — | 2021 | → |
| Large-scale collaboration in ENIGMA-EEG: A perspective on the meta-analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity. | Smit DJA et al. | — | 2021 | → |
| The association of polygenic risk for schizophrenia, bipolar disorder, and depression with neural connectivity in adolescents and young adults: examining developmental and sex differences. | Meyers JL et al. | — | 2021 | → |
| Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood. | Meyers JL et al. | — | 2019 | → |
| A KCNJ6 gene polymorphism modulates theta oscillations during reward processing. | Kamarajan C et al. | — | 2017 | → |