Genetic influences vary by age and sex: Trajectories of the association of cholinergic system variants and theta band event related oscillations.
- Authors
- Chorlian, David B; Meyers, Jacquelyn L; Manz, Niklas; Zhang, Jian; Kamarajan, Chella; Pandey, Ashwini; Wang, Jen-Chyong; Plawecki, Martin; Edenberg, Howard; Goate, Alison; Tischfield, Jay; Porjesz, Bernice
- Year
- 2023
- Journal
- bioRxiv : the preprint server for biology
- PMID
- 36909650
- DOI
- 10.1101/2023.02.27.530318
- PMCID
- PMC10002625
To characterize systemic changes in genetic effects on brain development, the age variation of the associations of cholinergic genetic variants and theta band event-related oscillations (EROs) was studied in a sample of 2140 adolescents and young adults, ages 12 to 25 from the COGA prospective study. The theta band EROs were elicited in visual and auditory oddball (target detection) tasks and measured by EEG recording. Associations were found to vary with age, sex, task modality (auditory or visual), and scalp locality. Seven of the twenty-one muscarinic and nicotinic cholinergic SNPs studied in the analysis, from , , , and , had significant effects on theta band EROs with considerable age spans for some sex-modality combination. No SNP-age-modality combination had significant effects in the same direction for males and females. Results suggest that nicotinic receptor associations are stronger before age 18, while muscarinic receptor associations are stronger after age 18.
Theta ERO trajectories.Theta ERO total power trajectory means in auditory (left column) and visual (right column) modalities presented in two views: Top row: Development curves; Bottom row: Rates of change of development curves: 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 more clearly illustrate the decrease in absolute value of the slopes with time. Line styles and colors of the bottom graph follow the legend in the top row.
Examples of Association Trajectories:Rows 1 and 3: Genotypic effects of Cholinergic SNPs on Frontal Auditory ERO trajectories from regression model. Solid: Males, Dashed: Females; Blue: 0 Major Alleles, Green: 1 Major Allele, Red: 2 Major Alleles. Rows 2 and 4: Genotypic association effect size (of major allele) trajectories: Blue: Male; Red: Female. Thicker lines indicate significant effect sizes, which correspond to greater inter-allelic distances in Rows 1 and 3
Identification of significant SNPs.Significant SNP-phenotype associations in the auditory modality. Color coding indicates signed value of significant median effect sizes over 3 year age ranges and all scalp locations.
Significant sex differences in association.Significant SNP-phenotype male-female differences in associations in the auditory and visual modalities. Color coding indicates signed value of significantly different (male - female) median effect sizes over 3 year age ranges and all scalp locations.
Identification of significant SNPs from the covariance structure of the genotype-phenotype associations.SNPs associated with phenotypic variance determined by the first component from age-specific sparse PCA. The sparsity constraint limits number of SNPs to parallel control by FDR threshold.
Discrimination of phenotypes by genotypic profile.Age specific phenotype-sex pairs for four age ranges in the space defined by the first two principal components of SNP profiles from age-specific sparse PCA. The positions of the phenotypes are particular to the individual plots, since the axes differ for each plot.
Median p-value.
Permutation test results.
Sparse PCA comparison with bootstrap frequency of occurance.
| # | Section | Preview |
|---|---|---|
| 40 | Statistical Methodology for the Analysis of Association Trajectories — Identification of significant SNPs — Significant SNPs identified by concentration of effect sizes | mean and standard deviations over all the pseudo-SNPs in each of the permutation procedures are… |
| 41 | Statistical Methodology for the Analysis of Association Trajectories — Identification of significant SNPs — Significant SNPs identified by concentration of effect sizes | The permutation tests are scale-free, and their use to identify important SNPs depends upon the… |
| 42 | Statistical Methodology for the Analysis of Association Trajectories — Identification of significant SNPs — Significant SNPs identified by concentration of effect sizes | Absolute values of effect sizes follow a folded normal distribution with variance 0.0025… |
| 43 | Statistical Methodology for the Analysis of Association Trajectories — Identification of significant SNPs — Significant SNPs identified by concentration of effect sizes | Any selection of SNP-age-phenotype combinations by thresholding of permutation scores will result in… |
| 44 | Statistical Methodology for the Analysis of Association Trajectories — Identification of SNPs contributing to Phenotypic Variance | Principal component analysis was not applied to the data set corresponding to the entire age range… |
| 45 | Statistical Methodology for the Analysis of Association Trajectories — Analysis of sPCA results | Sparse principal component analysis (sPCA) was used to determine genotypic profiles which… |
| 46 | Statistical Methodology for the Analysis of Association Trajectories — Analysis of sPCA results | range combinations in the first sPCA component of the 1000 bootstrap samples determined, as well as… |
| 47 | Statistical Methodology for the Analysis of Association Trajectories — Retrospective view | Further reflection on the these topics suggest that a multiscale approach, that is, with the… |
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External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Non-linear development of EEG coherence in adolescents and young adults shown by the analysis of neurophysiological trajectories and their covariance | Chorlian DB et al. | — | 2024 | — |