Table 1 Top 10 CpGs in sex-stratified analysis. Shown are CpGs that are highly significant in one sex (FDR < 0.05), but not significant (P-value > 0.05) in the other sex. For each CpG, annotations include the location of the CpG based on hg19/GRCh37 genomic annotation (chr, position), Illumina gene annotations, nearby genes based on GREAT, and chromatin state. The inverse-variance weighted meta-analysis regression model results include estimated effect size (estimate) where CpGs that are hyper-methylated in samples with AD neuropathology have positive values, and its associated standard error (se), P-value, and false discovery rate (FDR) for multiple comparison corrections. Bold indicates a significant association at 5% FDR
From: Sex-specific DNA methylation differences in Alzheimer’s disease pathology
cpg | Annotations | Female samples | Males samples | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
chr | Position | Illumina | GREAT (distance to TSS) | chromatin state | estimate | se | P-value | FDR | estimate | se | P-value | FDR | |
Significant only in female samples | |||||||||||||
cg09502865 | chr16 | 88600155 | ZFPM1 | ZC3H18(− 36633); ZFPM1(+ 80431) | Active TSS | 0.179 | 0.028 | 2.50E−10 | 1.15E−04 | 0.094 | 0.034 | 4.46E−01 | 9.64E−01 |
cg05235171 | chr11 | 117958104 | TMPRSS4 | TMPRSS4(+ 10301); SCN4B(+ 65430) | Quiescent/Low | − 0.168 | 0.029 | 7.61E−09 | 6.99E−04 | − 0.025 | 0.033 | 4.47E−01 | 9.64E−01 |
cg15610437 | chr19 | 827821 | AZU1 | AZU1(− 4) | Weak Repressed PolyComb | − 0.155 | 0.029 | 5.45E−08 | 1.99E−03 | − 0.090 | 0.034 | 9.79E−02 | 8.25E−01 |
cg13572782 | chr18 | 74799495 | MBP | MBP(+ 45229); ZNF236(+ 263380) | Active TSS | 0.157 | 0.029 | 5.75E−08 | 1.99E−03 | 0.047 | 0.036 | 1.90E−01 | 8.92E−01 |
cg17881200 | chr7 | 27138850 | HOXA1(− 3258) | Repressed PolyComb | 0.152 | 0.029 | 1.41E−07 | 2.98E−03 | 0.131 | 0.034 | 6.22E−02 | 7.73E−01 | |
cg22632947 | chr17 | 64787784 | PRKCA | CACNG5(− 43450); PRKCA(+ 488841) | Flanking Active TSS | − 0.139 | 0.026 | 1.50E−07 | 3.00E−03 | − 0.005 | 0.028 | 8.57E−01 | 9.95E−01 |
cg15467503 | chr4 | 1727234 | TACC3 | TMEM129(− 4177); TACC3(+ 3969) | Weak transcription | − 0.146 | 0.028 | 1.81E−07 | 3.45E−03 | − 0.083 | 0.034 | 1.33E−01 | 8.59E−01 |
cg26033526 | chr6 | 32819858 | TAP1 | PSMB9(− 2079); TAP1(+ 1896) | Genic enhancers | 0.148 | 0.029 | 2.64E−07 | 4.18E−03 | − 0.021 | 0.034 | 5.23E−01 | 9.73E−01 |
cg08363067 | chr16 | 16170085 | ABCC1 | ABCC1(+ 126652); ABCC6(+ 147235) | Weak transcription | − 0.120 | 0.024 | 7.68E−07 | 7.32E−03 | − 0.050 | 0.028 | 7.41E−02 | 7.94E−01 |
cg12926693 | chr6 | 36665611 | RAB44(− 17644); CDKN1A(+ 19125) | Quiescent/Low | − 0.149 | 0.030 | 8.59E−07 | 7.32E−03 | − 0.067 | 0.035 | 5.19E−02 | 7.52E−01 | |
Significant only in male samples | |||||||||||||
cg07687398 | chr3 | 53198666 | PRKCD | PRKCD(+ 3531); TKT(+ 91371) | Weak transcription | 0.052 | 0.030 | 8.63E−02 | 8.19E−01 | 0.183 | 0.035 | 1.16E−07 | 9.88E−03 |
cg10513118 | chr11 | 118047203 | SCN2B | SCN2B(+ 184) | Active TSS | 0.038 | 0.030 | 2.01E−01 | 9.17E−01 | 0.172 | 0.033 | 1.42E−07 | 9.88E−03 |
cg21253952 | chr8 | 143662999 | ARC(+ 33833); BAI1(+ 132209) | Weak Repressed PolyComb | − 0.019 | 0.030 | 5.33E−01 | 9.84E−01 | 0.169 | 0.034 | 4.44E−07 | 1.53E−02 | |
cg18281939 | chr5 | 77783895 | LHFPL2 | SCAMP1(+ 127557); LHFPL2(+ 160752) | Weak transcription | − 0.022 | 0.029 | 4.55E−01 | 9.76E−01 | − 0.179 | 0.036 | 6.26E−07 | 1.79E−02 |
cg11809272 | chr6 | 31409361 | HLA-B(− 84398); MICB(− 56530) | Quiescent/Low | − 0.001 | 0.031 | 9.77E−01 | 1.00E + 00 | 0.161 | 0.033 | 9.08E−07 | 2.17E−02 | |
cg15952933 | chr7 | 1899886 | MAD1L1 | ELFN1(+ 172132); MAD1L1(+ 372991) | Weak transcription | − 0.058 | 0.033 | 7.56E−02 | 8.00E−01 | − 0.156 | 0.032 | 9.48E−07 | 2.17E−02 |
cg11614451 | chr3 | 160167729 | TRIM59 | ENSG00000248710(− 113); TRIM59(− 113) | Flanking Bivalent TSS/Enh | − 0.041 | 0.029 | 1.56E−01 | 8.92E−01 | − 0.150 | 0.031 | 1.28E−06 | 2.44E−02 |
cg18942110 | chr15 | 91072797 | CRTC3 | CRTC3(− 502) | Active TSS | 0.031 | 0.030 | 3.06E−01 | 9.52E−01 | − 0.164 | 0.035 | 2.23E−06 | 3.19E−02 |
cg01655008 | chr14 | 93652954 | C14orf109 | MOAP1(− 1687); TMEM251(+ 1597) | Transcr. at gene 5′ and 3' | − 0.042 | 0.029 | 1.51E−01 | 8.89E−01 | − 0.152 | 0.032 | 2.54E−06 | 3.33E−02 |
cg02331272 | chr11 | 66964208 | KDM2A | ADRBK1(− 69672); KDM2A(+ 77051) | Weak transcription | 0.058 | 0.030 | 1.10E−01 | 8.52E−01 | − 0.166 | 0.036 | 2.99E−06 | 3.52E−02 |