Power comparison between CCRET and PLINK 1-sided tests for simulation I-A: between-locus heterogeneity of the dosage simulation.

<p>As detailed in section “Simulation Design”, we considered 6 heterogeneity models with different proportions of risk-associated (<math><msubsup><mrow><mi>β</mi></mrow><mrow><mi>m</mi></mrow><mrow><mi>D</mi><mi>S</mi><mo>.</mo><mo>•</mo></mrow></msubsup><mo>></mo><mn>0</mn></math>) or protective (<math><msubsup><mrow><mi>β</mi></mrow><mrow><mi>m</mi></mrow><mrow><mi>D</mi><mi>S</mi><mo>.</mo><mo>•</mo></mrow></msubsup><mo><</mo><mn>0</mn></math>) effects among causal loci. Black <b>O</b> line: CCRET; Blue <b>Δ</b>: PLINK 1-sided test analyzing deletions and duplications combined; Green <b>+</b>: PLINK 1-sided test analyzing only duplications; Magenta <b>x</b>: PLINK 1-sided test analyzing only deletions.</p

Power comparison between CCRET and PLINK 2-sided tests for simulation II-B: within-locus heterogeneity of the GI simulation, under 3 heterogeneity models as detailed in section “Simulation Design”.

<p>Black <b>O</b> line: CCRET; Blue <b>Δ</b>: PLINK 2-sided test analyzing deletions and duplications combined; Green <b>+</b>: PLINK 2-sided test analyzing only duplications; Magenta <b>x</b>: PLINK 2-sided test analyzing only deletions.</p

Type I error rates for evaluating dosage effects (nominal alpha = 0.05).

<p>*: Type I error rates based on PLINK 2-sided tests</p><p>**: Type I error rates in parentheses are based on PLINK 1-sided tests.</p><p>Type I error rates for evaluating dosage effects (nominal alpha = 0.05).</p

Type I error rates for evaluating GI effects (nominal alpha = 0.05).

<p>Type I error rates for evaluating GI effects (nominal alpha = 0.05).</p

Performance evaluation of the CCRET method.

<p>“Between-locus”: between-locus heterogeneity; “Within-locus”: within-locus heterogeneity.</p

Power comparison between CCRET and PLINK 2-sided tests for simulation I-B: within-locus heterogeneity of the dosage simulation, under 5 heterogeneity models as detailed in section “Simulation Design”.

<p>Black <b>O</b> line: CCRET; Blue <b>Δ</b>: PLINK 2-sided test analyzing deletions and duplications combined; Green <b>+</b>: PLINK 2-sided test analyzing only duplications; Magenta <b>x</b>: PLINK 2-sided test analyzing only deletions.</p

Power comparison between CCRET and PLINK 2-sided tests for simulation II-A: between-locus heterogeneity of the GI simulation, under 6 heterogeneity models as detailed in section “Simulation Design”.

<p>Black <b>O</b> line: CCRET; Blue <b>Δ</b>: PLINK 2-sided test analyzing deletions and duplications combined; Green <b>+</b>: PLINK 2-sided test analyzing only duplications; Magenta <b>x</b>: PLINK 2-sided test analyzing only deletions.</p

Test p-values for evaluating dosage effects based on schizophrenia data.

<p>DUP: duplications. DEL: deletions. Case (or control) CNV rate = the total number of CNVs in cases (or controls) divided by the total number of cases (or controls). Case/control ratio = Case CNV rate divided by control CNV rate. CNVR: copy number variation region. Pval_PLINK: 2-sided p-values based on 10,000 permutations and permuting phenotype labels within genotyping batches (asymptotic p-values were similar). Pval_CCRET: 2-sided p-values based on the Davies (1980) method.</p><p>Test p-values for evaluating dosage effects based on schizophrenia data.</p

Trivariate ADE Cholesky decomposition for Flow Proneness (FP), Behavioural Inhibition (BI), and Locus of Control (LOC) showing non-significant pathways (dashed lines) for all additive (A) and most dominant (D) genetic influences indicating low power to distinguish between A and D.

<p>Trivariate ADE Cholesky decomposition for Flow Proneness (FP), Behavioural Inhibition (BI), and Locus of Control (LOC) showing non-significant pathways (dashed lines) for all additive (A) and most dominant (D) genetic influences indicating low power to distinguish between A and D.</p

Full Cholesky decomposition showing genetic (G) and environmental (E) influences on the relationship between Flow Proneness (FP), Behavioral Inhibition (BI), and Locus of Control (LOC).

<p>Non-significant pathways in the model (<i>p</i>>0.05) were retained for completeness and are shown as dashed lines.</p