Table 2 Top 10 and 6 DMRs in sex-stratified analysis. Shown are DMRs that are highly significant in one sex (FDR < 0.05), but not significant (P-value > 0.05) in another sex. Only 6 DMRs satisfied these criteria in male samples. For each DMR, annotations include the location of the DMR based on hg19/GRCh37 genomic annotation (DMR), Illumina gene annotations, nearby genes based on GREAT, and chromatin state. The inverse-variance weighted meta-analysis regression models results based on coMethDMR include estimated effect size (estimate) where DMRs that are hyper-methylated in samples with AD neuropathology have positive values, its associated standard error (se), P-value, and false discovery rate (FDR) for multiple comparison corrections. Shown in bold are significant results with FDR < 0.05
From: Sex-specific DNA methylation differences in Alzheimer’s disease pathology
DMR | Annotations | Female samples | Male samples | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
Illumina | GREAT (distance to TSS) | chromatin state | estimate | se | P-value | FDR | estimate | se | P-value | FDR | |
Significant only in female samples | |||||||||||
chr5:27038605-27038836 | CDH9 | CDH9(− 28) | Active TSS;Flanking Active TSS | 0.128 | 0.024 | 1.87E−07 | 2.30E−03 | 0.077 | 0.027 | 2.74E−01 | 8.99E−01 |
chr15:31621629-31621843 | KLF13 | KLF13(+ 2678); OTUD7A(+ 325806) | Active TSS | 0.115 | 0.023 | 3.30E−07 | 2.30E−03 | 0.042 | 0.027 | 1.19E−01 | 8.07E−01 |
chr18:74799495-74799572 | MBP | MBP(+ 45191); ZNF236(+ 263418) | Active TSS | 0.138 | 0.028 | 5.81E−07 | 2.48E−03 | 0.049 | 0.033 | 1.30E−01 | 8.13E−01 |
chr7:45066738-45067057 | CCM2 | CCM2(+ 273) | Weak transcription | − 0.125 | 0.026 | 2.23E−06 | 6.20E−03 | − 0.090 | 0.027 | 5.51E−02 | 7.00E−01 |
chr13:67803895-67804060 | PCDH9 | PCDH9(+ 490) | Active TSS | − 0.088 | 0.019 | 5.04E−06 | 1.02E−02 | − 0.017 | 0.022 | 4.40E−01 | 9.50E−01 |
chr16:66969401-66969506 | CES2;FAM96B | FAM96B(− 1151); CES2(+ 1091) | Flanking Active TSS | 0.115 | 0.025 | 5.68E−06 | 1.02E−02 | 0.052 | 0.028 | 6.52E−02 | 7.28E−01 |
chr15:40268421-40268777 | EIF2AK4 | EIF2AK4(+ 42245); SRP14(+ 62790) | Active TSS | 0.125 | 0.028 | 7.12E−06 | 1.16E−02 | − 0.005 | 0.032 | 8.72E−01 | 9.94E−01 |
chr5:14492774-14492945 | TRIO | FAM105B(− 171997); TRIO(+ 349049) | Strong transcription | − 0.103 | 0.023 | 8.25E−06 | 1.24E−02 | − 0.009 | 0.029 | 7.49E−01 | 9.85E−01 |
chr17:56736571-56737118 | TEX14 | SEPT4(− 118666); TEX14(+ 32539) | Active TSS | − 0.070 | 0.016 | 9.13E−06 | 1.26E−02 | 0.017 | 0.017 | 3.20E−01 | 9.16E−01 |
chr17:46651722-46651952 | HOXB3 | HOXB3(− 20553); HOXB4(+ 5636) | Repressed PolyComb | 0.113 | 0.025 | 9.24E−06 | 1.26E−02 | 0.030 | 0.027 | 2.63E−01 | 8.97E−01 |
Significant only in male samples | |||||||||||
chr17:1173700-1173767 | BHLHA9 | BHLHA9(− 119) | Weak Repressed PolyComb | − 0.041 | 0.025 | 1.07E−01 | 8.23E−01 | − 0.118 | 0.026 | 5.08E−06 | 1.59E−02 |
chr11:68780866-68780984 | MRGPRF | MRGPRF(− 48) | Flanking Bivalent TSS/Enh | 0.032 | 0.024 | 1.80E−01 | 8.93E−01 | 0.112 | 0.026 | 1.16E−05 | 2.96E−02 |
chr12:52437299-52437571 | C12orf44(− 26320); NR4A1(+ 20819) | Enhancers | 0.009 | 0.017 | 5.93E−01 | 9.93E−01 | 0.075 | 0.017 | 1.38E−05 | 3.31E−02 | |
chr14:89017615-89017776 | PTPN21 | PTPN21(+ 3381); SPATA7(+ 165822) | Active TSS | 0.046 | 0.024 | 6.03E−02 | 7.31E−01 | 0.102 | 0.024 | 1.46E−05 | 3.31E−02 |
chr19:17691465-17691691 | GLT25D1 | COLGALT1(+ 25175); UNC13A(+ 107430) | Strong transcription | − 0.006 | 0.022 | 8.06E−01 | 1.00E + 00 | 0.107 | 0.025 | 2.47E−05 | 4.16E−02 |
chr6:32920567-32921233 | HLA-DMA | ENSG00000248993(− 1); HLA− DMA(− 1) | Flanking Active TSS; Active TSS; Quiescent/Low | − 0.045 | 0.024 | 3.16E−01 | 9.56E−01 | − 0.117 | 0.028 | 3.17E−05 | 4.78E−02 |