Additional file 1 of Quantitative phenotype scan statistic (QPSS) reveals rare variant associations with Alzheimer’s disease endophenotypes
Creators: name: Katsumata, Yuriko
name: Fardo, David W.
Publisher: name: figshare
Year: 2020
Subjects: subject: Genetics
subject: FOS: Biological sciences
subject: FOS: Biological sciences

description: Additional file 1: Supplementary Method 1. Scan statistics for the normal probability model developed by Kulldorff et al. [1]. Supplementary Method 2. Computing empirical p-values based on permutation test and approximation by a generalized Pareto distribution described by Knijnenburg et al. [2]. Table S1. Simulation scenario for type I error and power evaluations. Table S2. Frequency of the number of targeted sliding windows that produced the maximum value of lnLR̂W$$ \ln {\hat{LR}}_W $$ (n = 500). Table S3. Frequency of the number of targeted sliding windows that produced the maximum value of lnLR̂W$$ \ln {\hat{LR}}_W $$ (n = 1000). Table S4. Single variant associations on the significant window of TOMM40 (45,403,046 – 45,405,045) with log-transformed cerebrospinal fluid amyloid β 1–42 levels in ADNI. Table S5. Single variant associations on the significant window of intergenic region (45,412,796 – 45,413,295) with log-transformed cerebrospinal fluid amyloid β 1–42 levels in ADNI. Table S6. Single variant associations on the significant window of ARHGAP23 (36,637,321 – 36,638,320) with log-transformed cerebrospinal fluid phosphorylated tau levels in ADNI. Figure S1. Mean of continuous phenotype y in each scenario. Figure S2. Estimate of heritability in each scenario. Figure S3. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 200 bp, and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S4. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 200 bp, and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S5. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 200 bp, and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S6. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 500 bp, and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S7. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 500 bp, and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S8. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 500 bp, and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S9. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S10. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S11. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 500, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S12. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 200 bp, and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S13. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 200 bp, and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S14. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 200 bp, and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S15. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 500 bp, and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S16. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 500 bp, and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S17. Mean lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 500 bp, and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S18. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.2. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S19. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.4. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S20. Mean of lnLR̂W$$ \ln {\hat{LR}}_W $$ for n = 1000, cluster size = 2 kbp (containing 20% disease-related variants), and effect size c = 0.6. Each point represents the center position of each of the windows, and the blue vertical line indicates the center of the cluster position. Figure S21. Gene-based associations between rare variants located on chromosome 19 and log-transformed CSF amyloid β 1–42 levels in ADNI using the burden test, SKAT, and SKAT-O. The red horizontal line indicates the significance level with Bonferroni correction (α = 0.05/the number of genes on chromosome 19). Figure S22. Gene-based associations between rare variants located on chromosome 17 and log-transformed CSF phosphorylated tau levels in ADNI using the burden test, SKAT, and SKAT-O. The red horizontal line indicates the significance level with Bonferroni correction (α = 0.05/the number of genes on chromosome 17). Figure S23. QPSS p-values computed by the permutation with generalized Pareto distribution approximation for the associations between rare variants around APOE (± 10 Mbp) located on chromosome 19 and log-transformed CSF amyloid β 1-42 in ADNI. Figure S24. QPSS p-values computed by the permutation with generalized Pareto distribution approximation for the associations between rare variants around MAPT (± 10 Mbp) located on chromosome 17 and log-transformed CSF phosphorylated tau levels in ADNI. Figure S25. Single variant associations between rare variants around APOE (± 10 Mbp) located on chromosome 19 and log-transformed CSF amyloid β 1- 42 in ADNI.