Sensitivity and specificity of ASSET, BE, and CPASSOC for predicting trait-specific association.

<p>Sensitivity and specificity of ASSET, BE, and CPASSOC for predicting trait-specific association.</p

Power (K = 8, some effects in the opposite direction).

<p>The same simulation was conducted as previously except that the direction of some effects was opposite. The three panels (A), (B), and (C) from the top to the bottom represent when 25% of associated traits carry effects in the opposite direction and effect sizes were drawn from a normal distribution, a bimodal normal distribution, and a uniform distribution, respectively. In each graph, the Y-axis denotes the power of each method at an alpha level of 0.05 while the X-axis shows the number of truly associated traits. The panels (D), (E), and (F) summarize the power of the ten methods when 50% of effects are in opposite direction.</p

Power (K = 8, all effects in the same direction).

<p>In each simulation, a total of 10,000 summary association statistics were generated for eight traits. The numbers of subjects were 1,000 cases and 1,000 controls. The minor allele frequency (MAF) of each causal variant was 0.1. The three panels from the top to the bottom represent when the effect of the variant was drawn from a normal distribution, a bimodal normal distribution, and a uniform distribution. In each graph, the Y-axis denotes the power of each method at an alpha level of 0.05 while the X-axis shows the number of truly associated traits. All associated traits shared the effects in the same direction. Ten meta-analysis methods were separated into three groups each based on: (1) the fixed-effects model (blue hue), (2) the random-effects model (red hue), and (3) the p-value-based model (green hue).</p

Characterization of disorder-specific association for the top genome-wide significant loci from the meta-analysis of five neuropsychiatric disorders.

<p>Characterization of disorder-specific association for the top genome-wide significant loci from the meta-analysis of five neuropsychiatric disorders.</p

Meta analysis results of GWAS data with shared controls.

<p>Three control sample overlapping scenarios (0%, 50%, 100% overlapping) were set up to be used in the association study of both disorders. Total of four methods (ASSET1, ASSET2, CPASSOC, WICS) that are able to control overlapping samples between studies were compared with standard fixed-effect method (FEMA) for their performance in this analysis. The Y-axis denotes number of genome–wide significant loci.</p

Sample Characteristics.

<p>All participants who completed any of the six social cognition or social affiliation measures also completed the childhood experiences questionnaire. Different participants completed different social cognition/affiliation measures to minimize the burden of testing for each individual and thus minimize participant attrition. See “Web Administration and Sampling” for details of sampling procedures.</p><p>Sample Characteristics.</p

Associations between individual adversity exposure and social cognition / social affiliation measures.

<p>Results are given in terms of Cohen’s <i>d</i> by exposure (exposed versus non-exposed), controlling for influence of age, sex, and race/ethnicity on each dependent measure. Solid lines give 95% confidence intervals for Cohen’s d. Three asterisks indicate associations that were significant based on independent samples-t-test at p < 0.00033 (Bonferroni corrected for all comparisons), two asterisks indicate associations significant at p < 0.002 (Bonferroni corrected for number of adversities), and one asterisk indicates nominal significance at p < 0.05. As in the previous analysis, a number of childhood adversities robustly predicted theory of mind ability, social motivation, and social support, but none predicted face discrimination or face memory at above nominal levels of significance.</p

Summary scores and internal reliability for each social cognitive or social functioning measure.

<p>Scores for measures of social cognition (face emotion discrimination, face identity discrimination, face recognition memory, and theory of mind) are given in terms of mean and standard deviation of proportion correct. Scores for measures of social affiliation (social motivation and social support) are given in terms of mean and standard deviation of total scores, where the range of possible scores is given under the name of each measure. Reliability is reported in terms of Cronbach’s alpha, a measure of internal reliability or consistency.</p><p>Summary scores and internal reliability for each social cognitive or social functioning measure.</p

Summary of performance comparison for top fixed-effects models.

<p>Summary of performance comparison for top fixed-effects models.</p

Relationship between PCA-derived adversity components and six domains of social cognition and social affiliation.

<p>Results are given in terms of standardized regression coefficients, after controlling for influence of age, sex, and race/ethnicity on each dependent measure. Solid lines give 95% confidence intervals for each effect size estimate. Three asterisks indicate associations that were significant at p < 0.0021 (Bonferroni corrected for all comparisons), two asterisks indicate associations significant at p < 0.0125 (Bonferroni corrected for number of orthogonal comparisons in each model), and one asterisk indicates nominal significance at p < 0.05. Theory of mind ability, social motivation, and social support were all robustly associated with parental maltreatment—with reductions in scores across all three measures. Parental maladjustment was most associated with reduced theory of mind ability, parental neglect with reduced social support in adulthood, and sexual abuse / institutional care with reduced social motivation in adulthood. None of the face discrimination or face recognition memory showed more than nominal associations with childhood adversity.</p