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收到日期:2019年7月12日
接受日期:2019年7月22日
发布日期:2019年7月30日
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©2019 Kim A.这是一篇根据创作共用署名许可条款发布的开放获取的文章,该条款允许在任何媒体上无限制地使用、发布和复制,前提是注明原作者和来源
引用
Kim A(2019)改变了与男性神经性厌食症相关的DNA甲基化。整合分子Med 6 DOI:10.15761/IMM.1000376
法国雷恩遗传与发育研究所
科钦研究所,基因组学平台,Inserm U1016,法国巴黎
巴黎精神病学和神经科学研究所,Inserm U1266,法国巴黎
巴黎精神病学和神经科学研究所,Inserm U1266,法国巴黎
法国巴黎科钦医院青少年之家
科钦研究所,基因组学平台,Inserm U1016,法国巴黎
法国巴黎科钦医院青少年之家
巴黎精神病学和神经科学研究所,Inserm U1266,法国巴黎
法国巴黎笛卡尔大学圣安妮医院CMME。
法国雷恩遗传与发育研究所
巴黎精神病学和神经科学研究所,Inserm U1266,法国巴黎
分子遗传学和生物学实验室,Hôpital Cochin,HUPC,AP-HP,法国巴黎
内政部:10.15761/IMM.1000376
目的:神经性厌食症(AN)是一种严重的精神疾病,其特征是饮食行为异常,导致体重减轻和死亡率增加。虽然在女性中更常见,但估计有5%至10%的受影响患者为男性。到目前为止,男性AN的确切原因尚不清楚。与许多精神疾病一样,这可能是遗传、生物、心理和环境因素的综合作用。在这里,我们使用全基因组亚硫酸氢盐测序来确定男性个体的甲基组。
方法:我们通过亚硫酸氢盐测序3340894个生物相关CpG位点(Illumina TruSeqMethyl Capture EPIC试剂盒)对6例限制性类型男性患者进行分析。为减少环境影响,选择4名相关未受影响个体作为对照。
结果:在受限制类型影响的男性患者和未受影响的对照组之间进行比较,发现153个差异甲基化区域和1812个差异甲基化CpG,它们对应于与代谢和营养状态、精神状态和免疫功能相关的基因。此外,字符串网络分析软件发现亚网络,与MAPK信号通路、PI3K-Akt信号通路和神经营养素信号通路有关。
结论:我们的发现重复了几个关于几个靶基因的结果,如PRKAG2,RPTOR,ICAM5先前在女性AN中发现,并发现了涉及PI3K Akt和神经营养素信号通路的新信号通路在AN中受到干扰。
神经性厌食症,限制性厌食症,亚硫酸氢盐全基因组测序
神经性厌食症(AN)是一种复杂的神经精神障碍,其特征是体重减轻,并强烈害怕体重增加。对AN家族和双胞胎的研究表明,遗传和环境因素在AN发病机制中起重要作用。双胞胎研究估计遗传率为~56%[1]。然而,虽然候选基因研究和全基因组关联研究(GWAS)发现了一些基因,但在其他研究中往往无法复制[2-5]。同样的观察发现,重度抑郁症与AN[6]有共同的遗传和环境风险因素。事实上,患有AN的年轻人患抑郁症的风险很高。表观遗传学和环境因素可能在AN和重度抑郁障碍[8]的发生发展中发挥重要作用。最近,一项全基因组DNA甲基化研究在活跃的AN、缓解的AN和非AN对照的女性中进行。对这三个组的整体分析显示,有295个差异甲基化位点(DMS),代表277个基因。一些已鉴定的基因与营养、骨骼和组织健康、免疫功能/炎症、一般或转录过程以及胶质细胞-神经元相互作用有关。
由于AN在女性中的发病率是男性的九倍,关注性别特异性可能有助于揭示其整体性质。因此,我们建议对几个男性AN患者进行分析,部分支持最近的发现,并确定新的疾病相关途径。
我们分析了6例男性AN限制性型患者3.3 M以上的生物相关CpGs (Illumina TruSeqMethyl Capture EPIC kit)。该方法捕获3,340,894个CpG位点,包括26,981个CpG岛(107 Mb),包括美国医学遗传学学院(American College of Medical Genetics, ACMG)基因,编码已知与癌症有关的基因,编码Ensemble 70的外显子,以及定义为高兴趣和难以测序的100个启动子。为了减少环境影响,选择4个相关的未受影响的个体——两个AN个体的父母——作为对照。简单地说,根据制造商协议(使用TrueSeq DNA甲基化试剂盒(cat。EGMK81312, Illumina公司,圣地亚哥,CA), NEXTflex亚硫酸氢盐测序试剂盒(猫。519 - 02)和24 NEXTflex亚硫酸氢盐测序条形码(猫。511913))。pcr扩增后,亚硫酸氢盐处理的文库聚集在V3对端读流式细胞上,并在Illumina NextSeq500系统(Illumina)上测序100个周期。Fastq文件是使用Illumina的软件CASAVA v1.8.2生成的。原始fastq读由一个自定义管道处理,该管道包括:(i)为pass过滤器读过滤原始fastq读,(ii) Trim Galore修剪适配器序列,(iii)使用Bismark来引用人类基因组hg19执行基因组比对,以及(iv)由Bismark脚本进行甲基化调用(https://github.com/nf-core/methylseq).用R包methyKit对DNA[10]进行分析和注释。在校正潜在混杂因素并排除与年龄相关的CpG后,AN个体与对照组之间出现了差异。我们最初研究了AN患者和对照组之间的差异甲基化区域(DMRs),使用了一种计算算法MethylKit,该算法具有严格的统计截断q值(FDR调整p值<0.01),且甲基化变化至少为25%。
这种方法使我们能够在AN中识别出总共153个DMR(表1)。其中53个DMR是低甲基化的,100个是高甲基化的,这表明个体中有更多的基因区域倾向于甲基化,类似于先前的观察[9]。我们进一步检查了差异甲基化CpG(DMC)的基因组分布.与对照组相比,共有1812个DMC位点在AN患者中被确定(补充表1)。在1812个DMC中,748个是低甲基化的,而1065在AN样本中发生了高甲基化。在这1812个dmc中,有216个功能基因区域包含至少2个dmc。有趣的是,当我们将我们的dmc列表与Steiger及其同事的短列表进行比较时,在两个列表中都发现了32个基因(Supplementary Table 2)[9]。此外,在重度抑郁症患者中发现的100个差异甲基化位置中,我们的研究也发现了6个(Gng4 slc39a12 crtac1 myo7a NTM和RMST),其中4个在神经突延伸和神经发生中起作用(GNG4 SLC39A12,特种加工和RMST)[8].
表1。使用Illumina TruSeq甲基捕获EPIC试剂盒的预定义区域鉴定差异甲基化区域(DMR),该试剂盒在ANcases和对照组之间呈现至少25%的甲基化差异(柱改变)q值(FDR校正p值)阈值为0.01
DMR |
空空的 |
Nb基因 |
基因 |
p价值 |
问价值 |
改变 |
chrX_114502896_114503051 |
chrX |
0 |
- |
2.22451 e15汽油 |
3.71584E-14 |
59.78484933 |
chr14_54375093_54375328 |
chr14 |
1 |
AL138479。 |
2.65207 e-24 |
1.18277 e-22 |
48.00682879 |
chr8_80036078_80036321 |
chr8 |
0 |
- |
2.44128 e-36 |
2.55548 e-34 |
46.08190008 |
chr11_79289117_79289197 |
chr11 |
0 |
- |
2.09678E-48 |
3.89352E-46 |
44.01889299 |
chr2_165342265_165342368 |
chr2 |
1 |
GRB14 |
5.17941E-11 |
4.44995平台以及 |
43.62139918 |
chr5_118811413_118811668 |
chr5 |
2 |
HSD17B4 | snoU1 |
4.63731E-11 |
4.01928平台以及 |
43.59922516 |
chr19_45113900_45114110 |
chr19 |
2 |
CEACAM22P | IGSF23 |
9.32156 e-32 |
7.39337E-30 |
40.63822929 |
chr12_39885082_39885307 |
chr12 |
0 |
- |
1.48466E-54 |
3.57503E-52 |
40.49521423 |
chr11_99564881_99564954 |
chr11 |
1 |
CNTN5 |
9.37129E-15 |
1.42916E-13 |
39.62334329 |
chr20_46228572_46228783 |
chr20 |
1 |
NCOA3 |
1.11712 e-13 |
1.47266 e-12 |
39.56217898 |
chr12_9507242_9507307 |
chr12 |
0 |
- |
1.05726 e-24 |
4.90641 e-23 |
38.46786372 |
chr2_238213149_238213414 |
chr2 |
0 |
- |
1.58339 e-06 |
5.42033 e-06 |
37.58090232 |
chr9_88891303_88891317 |
chr9 |
1 |
ISCA1 |
1.08415 e-06 |
3.8617E-06 |
37.31409719 |
chr7_134279040_134279370 |
chr7 |
0 |
- |
7.42127 e-19 |
1.90865 e-17 |
36.8404498 |
chr11_125477842_125477944 |
chr11 |
1 |
STT3A |
1.37342E-52 |
3.02928 e-50 |
36.14363165 |
chr4_85873367_85873551 |
chr4 |
1 |
WDFY3 |
8.771 e-29 |
5.54172 e-27 |
35.86458464 |
chr1_228243499_228243750 |
chr1 |
1 |
WNT3A |
7.15126 e-21 |
2.28614E-19 |
35.584194 |
chr2_131046231_131046636 |
chr2 |
5 |
MTND4P2 | MTND5P2 | MTND6P | AC068137.1 | AC068137.1 |
1.32673 e-40 |
1.75348E-38 |
35.46103678 |
chr7_39723763_39723940 |
chr7 |
1 |
拉拉 |
2.01448 e-11 |
1.85339E-10 |
34.0085943 |
chr6_132297421_132297621 |
chr6 |
1 |
RP11-69I8。 |
0.001384883 |
0.002169711 |
33.37310303 |
chr3_108880309_108880502 |
chr3 |
0 |
- |
7.64309E-11 |
6.36725平台以及 |
33.06601128 |
chr1_66753890_66754101 |
chr1 |
1 |
PDE4B |
0.00182074 |
0.00275054 |
32.96104032 |
chr2_66654487_66654810 |
chr2 |
2 |
MEIS1-AS3 | MEIS1 |
2.10022 e - 69 |
7.72486 e - 67 |
32.72071839 |
chr5_97764439_97764614 |
chr5 |
0 |
- |
0.000291866 |
0.000557559 |
32.43193392 |
chr9_115957266_115957508 |
chr9 |
1 |
FKBP15 |
1.69011E-15 |
2.87555E-14 |
32.29050602 |
chr15_50209373_50209588 |
chr15 |
1 |
ATP8B4 |
3.01371E-25 |
1.45926E-23 |
31.98261372 |
chr17_11608628_11608839 |
chr17 |
1 |
DNAH9 |
6.97091E-30 |
4.8207即使 |
31.79815222 |
chr4_3040168_3040507 |
chr4 |
2 |
GRK4 | rnu6 - 204 |
7.3598E-14 |
9.96918 e-13 |
31.65690685 |
chr6_88956453_88956584 |
chr6 |
0 |
- |
9.99041 e-12 |
9.68676E-11 |
31.54201058 |
chr21_15436054_15437354 |
chr21 |
3. |
AP001347.| ANKRD20A18 | RNA5SP48 |
0 |
0 |
31.16688815 |
chr3_49712243_49712522 |
chr3 |
4 |
BSN | APEH | MST1 | AC099668。 |
8.07314 e-25 |
3.79115 e-23 |
31.03180163 |
chr12_25264152_25264371 |
chr12 |
2 |
LRMP | CASC1 |
8.78331E-27 |
4.8313 e-25 |
30.29058703 |
chrX_9121569_9121778 |
chrX |
1 |
FAM9B |
0.000426217 |
0.000777831 |
30.08088109 |
chr3_84932517_84932772 |
chr3 |
2 |
LINC00971 | LINC02025 |
2.07283 e-18 |
5.07715E-17 |
29.94169954 |
chr7_123928236_123928461 |
chr7 |
2 |
rp5 - 921十六国集团。| rp11 - 264 k23。 |
3.518E-31 |
2.67311 e-29 |
29.91216787 |
chr9_106087270_106087465 |
chr9 |
1 |
LINC01492 |
8.36825 e-19 |
2.13729 e-17 |
29.78985686 |
chr5_120388958_120389191 |
chr5 |
2 |
AC008565.| CTD-2613O8。 |
7.61105E-44 |
1.17667E-41 |
29.58350371 |
chr11_8927411_8927650 |
chr11 |
2 |
ST5 | AKIP1 |
4.49366平台以及 |
3.25802 e-09 |
29.52623011 |
chr6_159572123_159572413 |
chr6 |
0 |
- |
7.42108 e-39 |
8.88692E-37 |
29.31934038 |
chr22_49625975_49626187 |
chr22 |
0 |
- |
2.92003E-11 |
2.61571E-10 |
29.27879223 |
chr12_9776968_9777167 |
chr12 |
2 |
LOC374443 | RNU6-700 |
1.12651E-09 |
7.58502E-09 |
29.08923252 |
chr3_170332310_170332590 |
chr3 |
1 |
SLC7A14-AS1 |
1.8717E-08 |
9.81278 e-08 |
29.01098901 |
chr4_77986307_77986536 |
chr4 |
1 |
CCNI |
3.91084 e-14 |
5.48555E-13 |
28.97085991 |
chr22_42176013_42176129 |
chr22 |
1 |
MEI1 |
0.000206038 |
0.000410706 |
28.81962113 |
chr10_25240859_25240994 |
chr10 |
2 |
PRTFDC1 | RP11-165A20。 |
6.26124E-28 |
3.71906E-26 |
28.60587752 |
chr3_79966821_79966915 |
chr3 |
0 |
- |
1.15638平台以及 |
9.34284E-10 |
28.60217066 |
chr3_45649141_45649463 |
chr3 |
1 |
LIMD1 |
6.28165 e - 62 |
1.8899E-59 |
28.50314686 |
chr6_25166613_25166879 |
chr6 |
1 |
CMAHP |
2.17351E-96 |
1.46968 e - 93 |
28.37986243 |
chr3_152213629_152213846 |
chr3 |
1 |
RP11-362A9。 |
6.8342E-05 |
0.000155335 |
28.26746276 |
chr11_59836664_59836958 |
chr11 |
2 |
MS4A3 | rp11 - 736块。 |
3.63343 e-09 |
2.21257 e-08 |
28.0516934 |
chr20_14124320_14124383 |
chr20 |
1 |
MACROD2 |
1.40341 e-20 |
4.35847E-19 |
28.02413196 |
chr22_32728242_32728474 |
chr22 |
1 |
RP1-149A16.1 |
8.85421E-11 |
7.29047E-10 |
27.91646442 |
chr2_183106034_183106226 |
chr2 |
1 |
PDE1A |
9.65506E-09 |
5.3791E-08 |
27.85254866 |
chr6_118401762_118401938 |
chr6 |
2 |
SLC35F1 | LOC105377967 |
4.64459 e-19 |
1.22408E-17 |
27.79487179 |
CHR109136981491369992 |
chr10 |
1 |
PANK1 |
1.57036E-21 |
5.3785E-20 |
27.77056277 |
chr12_49121182_49121257 |
chr12 |
1 |
TEX49 |
8.24722 e-13 |
9.54004 e-12 |
27.60425962 |
chr5_95362159_95362388 |
chr5 |
1 |
LOC101929710 |
4.61645 e-19 |
1.21738E-17 |
27.51574796 |
chr17_16935456_16935522 |
chr17 |
0 |
- |
4.58885 e-09 |
2.74027 e-08 |
27.46293683 |
chr3_42093299_42093629 |
chr3 |
2 |
TRAK1 | rp11 - 193 i22。 |
6.20321E-37 |
6.69223E-35 |
27.41943731 |
chr3_149867507_14986767632 |
chr3 |
1 |
LOC105374313 |
3.07268 e-11 |
2.74327E-10 |
27.29693742 |
chrX_43503885_43504133 |
chrX |
0 |
- |
4.40393 e-09 |
2.64009 e-08 |
27.18926273 |
chr14_77035752_77035960 |
chr14 |
1 |
rp11 - 187 o7。 |
6.2288 e-12 |
6.23127E-11 |
27.15821169 |
chr10_52771069_52771259 |
chr10 |
1 |
PRKG1 |
3.87096E-16 |
7.14936E-15 |
27.04932754 |
chr2_38055293_38055466 |
chr2 |
1 |
LINC00211 |
7.48568E-28 |
4.4228E-26 |
27.03032591 |
chr1_108245511_108245769 |
chr1 |
1 |
VAV3 |
3.17027E-12 |
3.3165E-11 |
26.94594044 |
chr11_132891631_132891819 |
chr11 |
1 |
OPCML |
4.6077E-05 |
0.000109674 |
26.80024478 |
chr8_8538073_8538307 |
chr8 |
0 |
- |
6.60262 e-14 |
8.99085 e-13 |
26.64249158 |
chr8_107757803_107757980 |
chr8 |
1 |
OXR1 |
0.000716855 |
0.001224528 |
26.62186488 |
chr21_36250641_36250940 |
chr21 |
2 |
LOC100506403 | RUNX1 |
3.11176E-25 |
1.50565E-23 |
26.55673748 |
chr9_14910433_14910528 |
chr9 |
1 |
FREM1 |
8.33159E-21 |
2.64892E-19 |
26.53151371 |
chr3_10851357_10851586 |
chr3 |
1 |
SLC6A11 |
0.004410223 |
0.005890646 |
26.40737551 |
chr9_73216788_73217020 |
chr9 |
1 |
TRPM3 |
3.0921E-15 |
5.06212E-14 |
26.40133464 |
chr17_77906666_77906803 |
chr17 |
3. |
LINC01979 | LINC01978 | TBC1D16 |
3.90756 e-08 |
1.9197 e-07 |
26.38634157 |
chr15_101507155_101507328 |
chr15 |
1 |
LRRK1 |
5.16927E-09 |
3.05155E-08 |
26.37814064 |
CHR108798814987988359 |
chr10 |
1 |
GRID1 |
0.003497861 |
0.004828383 |
26.35618749 |
chr13_46978725_46978934 |
chr13 |
2 |
RUBCNL | rnu6 - 68 |
2.29746E-12 |
2.46329 e-11 |
26.04182226 |
chrX_149197068_149197285 |
chrX |
1 |
LINC00894 |
2.44211 e-07 |
1.01031 e-06 |
26.00779648 |
chr16_66453623_66453908 |
chr16 |
2 |
LINC00920 | BEAN1 |
3.68957 e-06 |
1.15579E-05 |
25.85630262 |
chr1_165186330_165186523 |
chr1 |
3. |
LMX1A | RP11-38C18。| RP11-38C18。 |
0.000275984 |
0.000530947 |
25.72822521 |
chr12_6662473_6662654 |
chr12 |
3. |
IFFO1 | RP5-940J5.| NOP2 |
9.5204E-29 |
6.00387 e-27 |
25.71991419 |
chr4_129308317_129308548 |
chr4 |
1 |
LINC02615 |
2.02201E-09 |
1.29361 e-08 |
25.68972744 |
chr4_102756899_102757268 |
chr4 |
1 |
银行1 |
8.27941 e-46 |
1.39081E-43 |
25.66642434 |
chr6_101852800_101852969 |
chr6 |
1 |
格里克2 |
1.14283 e-19 |
3.23959E-18 |
25.50742035 |
chr7_147500652_147500831 |
chr7 |
1 |
CNTNAP2 |
4.69478 e-06 |
1.43535E-05 |
25.47112462 |
chr2_130683180_130683508 |
chr2 |
2 |
PLAC9P1 | LINC01856 |
2.6716 e-16 |
5.03565 e15汽油 |
25.46823547 |
chr3_69157750_69157970 |
chr3 |
2 |
ARL6IP5 | LMOD3 |
6.39788 e-06 |
1.89017E-05 |
25.46542143 |
chr12_104676677_104676883 |
chr12 |
2 |
TXNRD1 | rp11 - 818 f20。 |
4.32249E-15 |
6.92567E-14 |
25.4273867 |
chr9_4375797_4376098 |
chr9 |
1 |
AL162419。 |
3.07166E-06 |
9.81114E-06 |
25.41113806 |
chr6_55377549_55377764 |
chr6 |
1 |
HMGCLL1 |
4.38355E-45 |
7.21874 e-43 |
25.36445879 |
chr8_80816076_80816210 |
chr8 |
0 |
- |
2.50289 e-06 |
8.16528 e-06 |
25.34385329 |
chr5_171810643_171810847 |
chr5 |
1 |
SH3PXD2B |
2.88223E-10 |
2.16508E-09 |
25.2488391 |
chr2_66648614_66648933 |
chr2 |
1 |
MEIS1-AS3 |
1.28929 e-22 |
4.90242E-21 |
25.21383356 |
chr14_96583490_96583604 |
chr14 |
0 |
- |
0.003078364 |
0.004325989 |
25.19935377 |
chr22_16864741_16864893 |
chr22 |
1 |
ABCD1P |
0.002259786 |
0.003313591 |
25.19298246 |
chr10_90483503_90483709 |
chr10 |
2 |
LIPK | KRT8P3 |
3.47526E-44 |
5.45461 e-42 |
25.15294597 |
chr6_7699982_7700169 |
chr6 |
0 |
- |
1.47903 e-12 |
1.64125E-11 |
25.12462285 |
chr3_195501977_195502276 |
chr3 |
1 |
MUC4 |
1.31243E-47 |
2.3649E-45 |
25.08813062 |
chr18_29303346_29303538 |
chr18 |
3. |
RN7SKP4 | LRRC37A7 | rp11 - 549的energisk b18。 |
1.62011 e-27 |
9.3655 e-26 |
25.03570419 |
chr3_95424692_95425326 |
chr3 |
0 |
- |
3.3968 e-14 |
4.80683 e-13 |
25.03516155 |
chr3_180102299_180102384 |
chr3 |
0 |
- |
9.13491 e-07 |
3.3066 e-06 |
25.01885857 |
chr22_35587422_35587713 |
chr22 |
2 |
LINC01399 | COX7BP |
1.08406E-10 |
8.79565平台以及 |
-25.01400968 |
chr20_36132841_36133069 |
chr20 |
1 |
BLCAP |
1.55091E-18 |
3.84306 e-17 |
-25.14666861 |
chr19_47082930_47083060 |
chr19 |
2 |
PPP5D1 | AC011551。 |
6.29188 e-21 |
2.02349 e-19 |
-25.24712874 |
chr19_49572906_49573157 |
chr19 |
4 |
NTF4 | CTB-60B18.1 | CTB-60B18.1 | KCNA7 |
5.89203 e-07 |
2.23171 e-06 |
-25.34019384 |
chr3_11489044_11489192 |
chr3 |
1 |
ATG7 |
7.90562E-10 |
5.47842E-09 |
-25.40198715 |
chr17_75631717_75631979 |
chr17 |
0 |
- |
1.84137E-05 |
4.85349 e-05 |
-25.53803605 |
chr1_19176711_19177105 |
chr1 |
2 |
TAS1R2 | RP13-279N23。 |
0.000375134 |
0.000695164 |
-25.58525242 |
chr11_5840963_5841191 |
chr11 |
2 |
TRIM5 | OR52N2 |
2.88714 e - 66 |
9.68772E-64 |
-25.69185678 |
chr2_55378165_55378300 |
chr2 |
0 |
- |
9.89458 e-19 |
2.51065E-17 |
-25.78431373 |
chr13_19315890_19316198 |
chr13 |
3. |
ZNF965 | LINC00417 | CYP4F34 |
8.90044 e-14 |
1.19079 e-12 |
-25.87364383 |
chr18_61669993_61670289 |
chr18 |
1 |
SERPINB8 |
8.41432 e - 63 |
2.5838E-60 |
-26.04262437 |
chr20_32885922_32886673 |
chr20 |
1 |
阿西 |
2.8332E-44 |
4.47838 e-42 |
-26.45197851 |
chr6_106252261_106252558 |
chr6 |
0 |
- |
6.2211E-107 |
4.9875 e - 104 |
-26.54101932 |
chr2_2538383849_25384399 |
chr2 |
3. |
EFR3B | rp11 - 509 e16天| POMC |
4.25503E-85 |
2.26062 e - 82 |
-26.70759651 |
chr4_131633369_131633569 |
chr4 |
0 |
- |
1.21778E-09 |
8.14225 e-09 |
-26.8218303 |
chr4_26789871_26790007 |
chr4 |
0 |
- |
9.76527 e-06 |
2.75795 e-05 |
-27.15229384 |
chr1_5537080_55370265 |
chr1 |
0 |
- |
1.33489E-60 |
3.89366 e-58 |
-27.2302102 |
chr19_45619267_45619497 |
chr19 |
2 |
标记4 | PPP1R37 |
3.61011 e-48 |
6.62101E-46 |
-27.29034787 |
chr16_33588844_33589010 |
chr16 |
1 |
ENPP7P13 |
8.03476 e-26 |
4.0933E-24 |
-27.38040136 |
chr4_15907926_15908145 |
chr4 |
0 |
- |
2.8442 e-50 |
5.76083E-48 |
-27.44818039 |
chr10_67155111_67155236 |
chr10 |
0 |
- |
4.83108 e-11 |
4.17264E-10 |
-27.80333564 |
chr17_4278292_4278786 |
chr17 |
1 |
UBE2G1 |
9.00939 e-24 |
3.82074 e-22 |
-27.82640422 |
chr11_11634408_116344147 |
chr11 |
0 |
- |
0.000326633 |
0.000615342 |
-27.8388828 |
chr19_34245878_34246069 |
chr19 |
1 |
CHST8 |
6.69284 e-06 |
1.96741E-05 |
-27.92649973 |
chr17_16864290_16864524 |
chr17 |
1 |
TNFRSF13B |
1.26001 e-12 |
1.41214 e-11 |
-28.2842299 |
chr11\u 82354426\u 82354705 |
chr11 |
2 |
MIR4300HG | rp11 - 179系。 |
6.09835 e-07 |
2.30172E-06 |
-29.18358119 |
chr5_153676389_153676633 |
chr5 |
1 |
GALNT10 |
1.43406 e - 68 |
5.14737 e - 66 |
-29.70725527 |
chr10_134778418_134779164 |
chr10 |
3. |
LINC01166 | LINC01167 | LINC01168 |
5.1864E-178 |
1.2399E-174 |
-29.73911375 |
chr8_36995835_36995986 |
chr8 |
1 |
MIR1268A |
3.40507 e-09 |
2.0846E-08 |
-29.75107115 |
chr2_213316451_213316721 |
chr2 |
1 |
ERBB4 |
3.25312 e-05 |
8.05895 e-05 |
-30.06050559 |
chr3_105601223_105601548 |
chr3 |
0 |
- |
3.99011 e-26 |
2.08106 e-24 |
-30.45696192 |
chr2_130693963_130694229 |
chr2 |
3. |
图9P1 | LINC01856 | AC079776。 |
1.8989 e - 114 |
1.6726 e - 111 |
-30.54653298 |
chr11_110986763_110986975 |
chr11 |
1 |
RP11-89C3。 |
0 |
0 |
-30.61868687 |
chr4_184296182_184296485 |
chr4 |
2 |
RP11-451F20.| AC093844。 |
3.2812 e - 82 |
1.64531 e - 79 |
-30.6235367 |
chr6_21452696_21452935 |
chr6 |
0 |
- |
4.66098E-09 |
2.77827 e-08 |
-30.7652865 |
chr14_56669107_56669307 |
chr14 |
1 |
PELI2 |
0.005344129 |
0.006946025 |
-31.10639369 |
chr13_25141770_2514291 |
chr13 |
3. |
TPTE2P6 | PSPC1P | RP11-556N21。 |
2.11697 e-25 |
1.04092 e-23 |
-31.10709988 |
chr2_238796929_238797268 |
chr2 |
1 |
匝道1 |
9.04001 e-24 |
3.83251 e-22 |
-31.35072812 |
chr17_6901611_6901751 |
chr17 |
4 |
ALOX12-AS1 | rp11 - 589 p10。| rp11 - 589 p10。| ALOX12 |
0.00014541 |
0.000302279 |
-31.60823695 |
chr15_79299672_79299707 |
chr15 |
1 |
RASGRF1 |
0.004476538 |
0.005967375 |
-32.72230999 |
chr1_223353214_223353363 |
chr1 |
1 |
RP11-239E10 |
7.13359 e-18 |
1.64468E-16 |
-33.00889209 |
chr1_113221602_113221746 |
chr1 |
2 |
CAPZA1 | MOV10 |
8.44636 e-34 |
7.62526 e-32 |
-33.03827068 |
chr19_21860552_21861267 |
chr19 |
1 |
rp11 - 420 k14。 |
1.3469E-284 |
1.127E-280 |
-33.08420719 |
chr2_145505959_145506291 |
chr2 |
2 |
TEX41 | AC023128。 |
2.36911E-23 |
9.63501 e-22 |
-33.13077409 |
chr21_29565178_29565285 |
chr21 |
1 |
LINC01695 |
0.000196292 |
0.000393653 |
-33.4915241 |
chr22_47442504_47442671 |
chr22 |
1 |
TBC1D22A |
2.44869E-31 |
1.87658E-29 |
-34.87001855 |
chr8_119449323_119449547 |
chr8 |
1 |
SAMD12 |
2.1869 e-06 |
7.23312 e-06 |
-36.3138769 |
chr3_6706652_6706860 |
chr3 |
2 |
AC069277.| GRM7-AS3 |
0.00028562 |
0.000547251 |
-39.63810451 |
chr8_129286309_129286584 |
chr8 |
0 |
- |
3.30084 e-09 |
2.02608 e-08 |
-39.75752508 |
chr12_64067778_64067878 |
chr12 |
3. |
MIR548Z | DPY19L2 | rp11 - 415 i12。 |
0.000389652 |
0.000718873 |
-40.8170893 |
CHR157118771771187868 |
chr15 |
2 |
LRRC49 | THAP10 |
0.004522921 |
0.006020138 |
-42.45762712 |
chr3_115099771_115100023 |
chr3 |
0 |
- |
0.002555418 |
0.003683188 |
-42.60471914 |
chr17_57187586_57187924 |
chr17 |
3. |
TRIM37 | AC099850。| SKA2 |
2.39899 e-60 |
6.93704 e-58 |
-46.21784352 |
识别的分子通路和功能可能受到甲基化改变的,我们去执行一项和KEGG通路富集分析最近的基因识别dmr(基因体内或在+ / - 10 kb的基因开始/结束网站)使用大卫生物信息学资源6.8 (https://david.ncifcrf.gov/)。使用“疾病”进行分类时,DMRs有5个图类(Benjamini校正后p值显著),较显著的图类是腰臀比(n=9计数,Benjamini 5.2 -3)、烟草使用障碍(37计数,Benjamini 2.8 -3)、化学依赖(n=40计数,Benjamini 1.2 -3)、代谢(n=49,Benjamini 3.1e-3)和神经学(32计数,Benjamini 3.8e-3)。
我们接下来聚焦于153 dmr,用String网络分析软件识别出一个子网络,与MAPK信号通路(hs04010, FDR 0.0026)、PI3K-Akt信号通路(hsa04151, FDR 0.0232)和神经营养因子信号通路(hsa04550, FDR 0.0251)(https://string-db.org/cgi/network.pl?taskId=07ri9Goe1SzI)(图1)。
图1。使用字符串软件构建的已鉴定蛋白质的蛋白质子网络,用于蛋白质富集分析(PPI富集值7.04e-08),显示甲基化异常状态(119个已鉴定DMR中的15个DMR,包括至少一个编码或非编码基因).每个节点代表一个蛋白质实体。基因本体识别了包括神经元分化(GO:0030182,FDR 8.15e-06)和行为(GO:0007610,FDR 0.00025)(黑色)在内的多个生物学过程的功能丰富,KEGG通路识别了包括MAPK信号通路(hs04010,FDR 0.0026)在内的多个通路的功能丰富(灰色正方形)、PI3K Akt信号通路(hsa04151,FDR 0.0232)(白色正方形)和神经营养素信号通路(hsa04550,FDR 0.0251)(灰色三角形)(https://string-db.org/cgi/network.pl?taskId=07ri9Goe1SzI)
据我们所知,本研究首次对6名男性AN患者进行全基因组DNA甲基化分析,使用高通量DNA甲基化测序覆盖人类基因组上的大量CpG位点。受限制性类型影响的患者显示出许多差异甲基化位点,其中与代谢和营养状态、精神状态和免疫功能相关的基因相对应的组间差异。当我们将我们的DMCs列表与Steiger及其同事在女性AN患者中获得的短列表进行比较时,在两个列表中都发现了32个基因[9]此外,由于抑郁症和神经性厌食症之间的相互作用是显著的,我们还发现了先前在重度抑郁症患者中发现的六个基因[8]考虑到我们的方法是基于全基因组甲基化测序的,我们还确定了其他与精神疾病有关的候选基因(Grid1, naaladl2-as3, pdzd, cep85l, grik3, slc7a14)、代谢调节(脂质、Zfp36l1, cerk, acsf3, eepd1;葡萄糖,KCNA7),最后是上瘾(GDE1、CCKAR、PDYN).此外,我们在全基因组关联研究中发现了少数与神经性厌食症相关的基因(Vgll4, grid1, wwox, camk1d, sorcs2) (https://www.ebi.ac.uk/gwas/search?query=anorexia%20nervosa)有趣的是,字符串网络分析软件揭示了与神经营养素信号通路相关的子网络(图1)。报告的数据,以及之前报告的脑源性神经营养因子,NTRK2和NTRK3,再次指出神经营养素信号基因是饮食行为的关键调节因子。
综上所述,我们的数据复制了一些关于几个靶基因的结果,例如PRKAG2,RPTOR,ICAM5之前讨论过[9],并发现了新的信号通路,包括PI3K-Akt和神经营养因子信号通路在神经性厌食症中被干扰。未来在男性AN患者身上的研究结果将是一个决定因素。
这项研究得到了国家医学研究所(INSERM)和罕见疾病基金会(高通量测序和罕见疾病项目,编号#11632)的支持。
作者声明他们没有利益冲突。
本次研究中的所有procédures均符合我国国家研究委员会的道德标准,并符合1964年赫尔辛基宣言及其后来的修正案。所有纳入研究的患者和家长均获得了知情的书面同意。
我们感谢这些家庭的热情参与以及来自不同医疗和精神病学中心的所有医生。
查看补充数据研究文章
收到日期:2019年7月12日
接受日期:2019年7月22日
发布日期:2019年7月30日
©2019 Kim A.这是一篇根据创作共用署名许可条款发布的开放获取的文章,该条款允许在任何媒体上无限制地使用、发布和复制,前提是注明原作者和来源
Kim A(2019)改变了与男性神经性厌食症相关的DNA甲基化。整合分子Med 6 DOI:10.15761/IMM.1000376
图1。使用字符串软件构建的已鉴定蛋白质的蛋白质子网络,用于蛋白质富集分析(PPI富集值7.04e-08),显示甲基化异常状态(119个已鉴定DMR中的15个DMR,包括至少一个编码或非编码基因).每个节点代表一个蛋白质实体。基因本体识别了包括神经元分化(GO:0030182,FDR 8.15e-06)和行为(GO:0007610,FDR 0.00025)(黑色)在内的多个生物学过程的功能丰富,KEGG通路识别了包括MAPK信号通路(hs04010,FDR 0.0026)在内的多个通路的功能丰富(灰色正方形)、PI3K Akt信号通路(hsa04151,FDR 0.0232)(白色正方形)和神经营养素信号通路(hsa04550,FDR 0.0251)(灰色三角形)(https://string-db.org/cgi/network.pl?taskId=07ri9Goe1SzI)
表1。使用Illumina TruSeq甲基捕获EPIC试剂盒的预定义区域鉴定差异甲基化区域(DMR),该试剂盒在ANcases和对照组之间呈现至少25%的甲基化差异(柱改变)q值(FDR校正p值)阈值为0.01
DMR |
空空的 |
Nb基因 |
基因 |
p价值 |
问价值 |
改变 |
chrX_114502896_114503051 |
chrX |
0 |
- |
2.22451 e15汽油 |
3.71584E-14 |
59.78484933 |
chr14_54375093_54375328 |
chr14 |
1 |
AL138479。 |
2.65207 e-24 |
1.18277 e-22 |
48.00682879 |
chr8_80036078_80036321 |
chr8 |
0 |
- |
2.44128 e-36 |
2.55548 e-34 |
46.08190008 |
chr11_79289117_79289197 |
chr11 |
0 |
- |
2.09678E-48 |
3.89352E-46 |
44.01889299 |
chr2_165342265_165342368 |
chr2 |
1 |
GRB14 |
5.17941E-11 |
4.44995平台以及 |
43.62139918 |
chr5_118811413_118811668 |
chr5 |
2 |
HSD17B4 | snoU1 |
4.63731E-11 |
4.01928平台以及 |
43.59922516 |
chr19_45113900_45114110 |
chr19 |
2 |
CEACAM22P | IGSF23 |
9.32156 e-32 |
7.39337E-30 |
40.63822929 |
chr12_39885082_39885307 |
chr12 |
0 |
- |
1.48466E-54 |
3.57503E-52 |
40.49521423 |
chr11_99564881_99564954 |
chr11 |
1 |
CNTN5 |
9.37129E-15 |
1.42916E-13 |
39.62334329 |
chr20_46228572_46228783 |
chr20 |
1 |
NCOA3 |
1.11712 e-13 |
1.47266 e-12 |
39.56217898 |
chr12_9507242_9507307 |
chr12 |
0 |
- |
1.05726 e-24 |
4.90641 e-23 |
38.46786372 |
chr2_238213149_238213414 |
chr2 |
0 |
- |
1.58339 e-06 |
5.42033 e-06 |
37.58090232 |
chr9_88891303_88891317 |
chr9 |
1 |
ISCA1 |
1.08415 e-06 |
3.8617E-06 |
37.31409719 |
chr7_134279040_134279370 |
chr7 |
0 |
- |
7.42127 e-19 |
1.90865 e-17 |
36.8404498 |
chr11_125477842_125477944 |
chr11 |
1 |
STT3A |
1.37342E-52 |
3.02928 e-50 |
36.14363165 |
chr4_85873367_85873551 |
chr4 |
1 |
WDFY3 |
8.771 e-29 |
5.54172 e-27 |
35.86458464 |
chr1_228243499_228243750 |
chr1 |
1 |
WNT3A |
7.15126 e-21 |
2.28614E-19 |
35.584194 |
chr2_131046231_131046636 |
chr2 |
5 |
MTND4P2 | MTND5P2 | MTND6P | AC068137.1 | AC068137.1 |
1.32673 e-40 |
1.75348E-38 |
35.46103678 |
chr7_39723763_39723940 |
chr7 |
1 |
拉拉 |
2.01448 e-11 |
1.85339E-10 |
34.0085943 |
chr6_132297421_132297621 |
chr6 |
1 |
RP11-69I8。 |
0.001384883 |
0.002169711 |
33.37310303 |
chr3_108880309_108880502 |
chr3 |
0 |
- |
7.64309E-11 |
6.36725平台以及 |
33.06601128 |
chr1_66753890_66754101 |
chr1 |
1 |
PDE4B |
0.00182074 |
0.00275054 |
32.96104032 |
chr2_66654487_66654810 |
chr2 |
2 |
MEIS1-AS3 | MEIS1 |
2.10022 e - 69 |
7.72486 e - 67 |
32.72071839 |
chr5_97764439_97764614 |
chr5 |
0 |
- |
0.000291866 |
0.000557559 |
32.43193392 |
chr9_115957266_115957508 |
chr9 |
1 |
FKBP15 |
1.69011E-15 |
2.87555E-14 |
32.29050602 |
chr15_50209373_50209588 |
chr15 |
1 |
ATP8B4 |
3.01371E-25 |
1.45926E-23 |
31.98261372 |
chr17_11608628_11608839 |
chr17 |
1 |
DNAH9 |
6.97091E-30 |
4.8207即使 |
31.79815222 |
chr4_3040168_3040507 |
chr4 |
2 |
GRK4 | rnu6 - 204 |
7.3598E-14 |
9.96918 e-13 |
31.65690685 |
chr6_88956453_88956584 |
chr6 |
0 |
- |
9.99041 e-12 |
9.68676E-11 |
31.54201058 |
chr21_15436054_15437354 |
chr21 |
3. |
AP001347.| ANKRD20A18 | RNA5SP48 |
0 |
0 |
31.16688815 |
chr3_49712243_49712522 |
chr3 |
4 |
BSN | APEH | MST1 | AC099668。 |
8.07314 e-25 |
3.79115 e-23 |
31.03180163 |
chr12_25264152_25264371 |
chr12 |
2 |
LRMP | CASC1 |
8.78331E-27 |
4.8313 e-25 |
30.29058703 |
chrX_9121569_9121778 |
chrX |
1 |
FAM9B |
0.000426217 |
0.000777831 |
30.08088109 |
chr3_84932517_84932772 |
chr3 |
2 |
LINC00971 | LINC02025 |
2.07283 e-18 |
5.07715E-17 |
29.94169954 |
chr7_123928236_123928461 |
chr7 |
2 |
rp5 - 921十六国集团。| rp11 - 264 k23。 |
3.518E-31 |
2.67311 e-29 |
29.91216787 |
chr9_106087270_106087465 |
chr9 |
1 |
LINC01492 |
8.36825 e-19 |
2.13729 e-17 |
29.78985686 |
chr5_120388958_120389191 |
chr5 |
2 |
AC008565.| CTD-2613O8。 |
7.61105E-44 |
1.17667E-41 |
29.58350371 |
chr11_8927411_8927650 |
chr11 |
2 |
ST5 | AKIP1 |
4.49366平台以及 |
3.25802 e-09 |
29.52623011 |
chr6_159572123_159572413 |
chr6 |
0 |
- |
7.42108 e-39 |
8.88692E-37 |
29.31934038 |
chr22_49625975_49626187 |
chr22 |
0 |
- |
2.92003E-11 |
2.61571E-10 |
29.27879223 |
chr12_9776968_9777167 |
chr12 |
2 |
LOC374443 | RNU6-700 |
1.12651E-09 |
7.58502E-09 |
29.08923252 |
chr3_170332310_170332590 |
chr3 |
1 |
SLC7A14-AS1 |
1.8717E-08 |
9.81278 e-08 |
29.01098901 |
chr4_77986307_77986536 |
chr4 |
1 |
CCNI |
3.91084 e-14 |
5.48555E-13 |
28.97085991 |
chr22_42176013_42176129 |
chr22 |
1 |
MEI1 |
0.000206038 |
0.000410706 |
28.81962113 |
chr10_25240859_25240994 |
chr10 |
2 |
PRTFDC1 | RP11-165A20。 |
6.26124E-28 |
3.71906E-26 |
28.60587752 |
chr3_79966821_79966915 |
chr3 |
0 |
- |
1.15638平台以及 |
9.34284E-10 |
28.60217066 |
chr3_45649141_45649463 |
chr3 |
1 |
LIMD1 |
6.28165 e - 62 |
1.8899E-59 |
28.50314686 |
chr6_25166613_25166879 |
chr6 |
1 |
CMAHP |
2.17351E-96 |
1.46968 e - 93 |
28.37986243 |
chr3_152213629_152213846 |
chr3 |
1 |
RP11-362A9。 |
6.8342E-05 |
0.000155335 |
28.26746276 |
chr11_59836664_59836958 |
chr11 |
2 |
MS4A3 | rp11 - 736块。 |
3.63343 e-09 |
2.21257 e-08 |
28.0516934 |
chr20_14124320_14124383 |
chr20 |
1 |
MACROD2 |
1.40341 e-20 |
4.35847E-19 |
28.02413196 |
chr22_32728242_32728474 |
chr22 |
1 |
RP1-149A16.1 |
8.85421E-11 |
7.29047E-10 |
27.91646442 |
chr2_183106034_183106226 |
chr2 |
1 |
PDE1A |
9.65506E-09 |
5.3791E-08 |
27.85254866 |
chr6_118401762_118401938 |
chr6 |
2 |
SLC35F1 | LOC105377967 |
4.64459 e-19 |
1.22408E-17 |
27.79487179 |
CHR109136981491369992 |
chr10 |
1 |
PANK1 |
1.57036E-21 |
5.3785E-20 |
27.77056277 |
chr12_49121182_49121257 |
chr12 |
1 |
TEX49 |
8.24722 e-13 |
9.54004 e-12 |
27.60425962 |
chr5_95362159_95362388 |
chr5 |
1 |
LOC101929710 |
4.61645 e-19 |
1.21738E-17 |
27.51574796 |
chr17_16935456_16935522 |
chr17 |
0 |
- |
4.58885 e-09 |
2.74027 e-08 |
27.46293683 |
chr3_42093299_42093629 |
chr3 |
2 |
TRAK1 | rp11 - 193 i22。 |
6.20321E-37 |
6.69223E-35 |
27.41943731 |
chr3_149867507_14986767632 |
chr3 |
1 |
LOC105374313 |
3.07268 e-11 |
2.74327E-10 |
27.29693742 |
chrX_43503885_43504133 |
chrX |
0 |
- |
4.40393 e-09 |
2.64009 e-08 |
27.18926273 |
chr14_77035752_77035960 |
chr14 |
1 |
rp11 - 187 o7。 |
6.2288 e-12 |
6.23127E-11 |
27.15821169 |
chr10_52771069_52771259 |
chr10 |
1 |
PRKG1 |
3.87096E-16 |
7.14936E-15 |
27.04932754 |
chr2_38055293_38055466 |
chr2 |
1 |
LINC00211 |
7.48568E-28 |
4.4228E-26 |
27.03032591 |
chr1_108245511_108245769 |
chr1 |
1 |
VAV3 |
3.17027E-12 |
3.3165E-11 |
26.94594044 |
chr11_132891631_132891819 |
chr11 |
1 |
OPCML |
4.6077E-05 |
0.000109674 |
26.80024478 |
chr8_8538073_8538307 |
chr8 |
0 |
- |
6.60262 e-14 |
8.99085 e-13 |
26.64249158 |
chr8_107757803_107757980 |
chr8 |
1 |
OXR1 |
0.000716855 |
0.001224528 |
26.62186488 |
chr21_36250641_36250940 |
chr21 |
2 |
LOC100506403 | RUNX1 |
3.11176E-25 |
1.50565E-23 |
26.55673748 |
chr9_14910433_14910528 |
chr9 |
1 |
FREM1 |
8.33159E-21 |
2.64892E-19 |
26.53151371 |
chr3_10851357_10851586 |
chr3 |
1 |
SLC6A11 |
0.004410223 |
0.005890646 |
26.40737551 |
chr9_73216788_73217020 |
chr9 |
1 |
TRPM3 |
3.0921E-15 |
5.06212E-14 |
26.40133464 |
chr17_77906666_77906803 |
chr17 |
3. |
LINC01979 | LINC01978 | TBC1D16 |
3.90756 e-08 |
1.9197 e-07 |
26.38634157 |
chr15_101507155_101507328 |
chr15 |
1 |
LRRK1 |
5.16927E-09 |
3.05155E-08 |
26.37814064 |
CHR108798814987988359 |
chr10 |
1 |
GRID1 |
0.003497861 |
0.004828383 |
26.35618749 |
chr13_46978725_46978934 |
chr13 |
2 |
RUBCNL | rnu6 - 68 |
2.29746E-12 |
2.46329 e-11 |
26.04182226 |
chrX_149197068_149197285 |
chrX |
1 |
LINC00894 |
2.44211 e-07 |
1.01031 e-06 |
26.00779648 |
chr16_66453623_66453908 |
chr16 |
2 |
LINC00920 | BEAN1 |
3.68957 e-06 |
1.15579E-05 |
25.85630262 |
chr1_165186330_165186523 |
chr1 |
3. |
LMX1A | RP11-38C18。| RP11-38C18。 |
0.000275984 |
0.000530947 |
25.72822521 |
chr12_6662473_6662654 |
chr12 |
3. |
IFFO1 | RP5-940J5.| NOP2 |
9.5204E-29 |
6.00387 e-27 |
25.71991419 |
chr4_129308317_129308548 |
chr4 |
1 |
LINC02615 |
2.02201E-09 |
1.29361 e-08 |
25.68972744 |
chr4_102756899_102757268 |
chr4 |
1 |
银行1 |
8.27941 e-46 |
1.39081E-43 |
25.66642434 |
chr6_101852800_101852969 |
chr6 |
1 |
格里克2 |
1.14283 e-19 |
3.23959E-18 |
25.50742035 |
chr7_147500652_147500831 |
chr7 |
1 |
CNTNAP2 |
4.69478 e-06 |
1.43535E-05 |
25.47112462 |
chr2_130683180_130683508 |
chr2 |
2 |
PLAC9P1 | LINC01856 |
2.6716 e-16 |
5.03565 e15汽油 |
25.46823547 |
chr3_69157750_69157970 |
chr3 |
2 |
ARL6IP5 | LMOD3 |
6.39788 e-06 |
1.89017E-05 |
25.46542143 |
chr12_104676677_104676883 |
chr12 |
2 |
TXNRD1 | rp11 - 818 f20。 |
4.32249E-15 |
6.92567E-14 |
25.4273867 |
chr9_4375797_4376098 |
chr9 |
1 |
AL162419。 |
3.07166E-06 |
9.81114E-06 |
25.41113806 |
chr6_55377549_55377764 |
chr6 |
1 |
HMGCLL1 |
4.38355E-45 |
7.21874 e-43 |
25.36445879 |
chr8_80816076_80816210 |
chr8 |
0 |
- |
2.50289 e-06 |
8.16528 e-06 |
25.34385329 |
chr5_171810643_171810847 |
chr5 |
1 |
SH3PXD2B |
2.88223E-10 |
2.16508E-09 |
25.2488391 |
chr2_66648614_66648933 |
chr2 |
1 |
MEIS1-AS3 |
1.28929 e-22 |
4.90242E-21 |
25.21383356 |
chr14_96583490_96583604 |
chr14 |
0 |
- |
0.003078364 |
0.004325989 |
25.19935377 |
chr22_16864741_16864893 |
chr22 |
1 |
ABCD1P |
0.002259786 |
0.003313591 |
25.19298246 |
chr10_90483503_90483709 |
chr10 |
2 |
LIPK | KRT8P3 |
3.47526E-44 |
5.45461 e-42 |
25.15294597 |
chr6_7699982_7700169 |
chr6 |
0 |
- |
1.47903 e-12 |
1.64125E-11 |
25.12462285 |
chr3_195501977_195502276 |
chr3 |
1 |
MUC4 |
1.31243E-47 |
2.3649E-45 |
25.08813062 |
chr18_29303346_29303538 |
chr18 |
3. |
RN7SKP4 | LRRC37A7 | rp11 - 549的energisk b18。 |
1.62011 e-27 |
9.3655 e-26 |
25.03570419 |
chr3_95424692_95425326 |
chr3 |
0 |
- |
3.3968 e-14 |
4.80683 e-13 |
25.03516155 |
chr3_180102299_180102384 |
chr3 |
0 |
- |
9.13491 e-07 |
3.3066 e-06 |
25.01885857 |
chr22_35587422_35587713 |
chr22 |
2 |
LINC01399 | COX7BP |
1.08406E-10 |
8.79565平台以及 |
-25.01400968 |
chr20_36132841_36133069 |
chr20 |
1 |
BLCAP |
1.55091E-18 |
3.84306 e-17 |
-25.14666861 |
chr19_47082930_47083060 |
chr19 |
2 |
PPP5D1 | AC011551。 |
6.29188 e-21 |
2.02349 e-19 |
-25.24712874 |
chr19_49572906_49573157 |
chr19 |
4 |
NTF4 | CTB-60B18.1 | CTB-60B18.1 | KCNA7 |
5.89203 e-07 |
2.23171 e-06 |
-25.34019384 |
chr3_11489044_11489192 |
chr3 |
1 |
ATG7 |
7.90562E-10 |
5.47842E-09 |
-25.40198715 |
chr17_75631717_75631979 |
chr17 |
0 |
- |
1.84137E-05 |
4.85349 e-05 |
-25.53803605 |
chr1_19176711_19177105 |
chr1 |
2 |
TAS1R2 | RP13-279N23。 |
0.000375134 |
0.000695164 |
-25.58525242 |
chr11_5840963_5841191 |
chr11 |
2 |
TRIM5 | OR52N2 |
2.88714 e - 66 |
9.68772E-64 |
-25.69185678 |
chr2_55378165_55378300 |
chr2 |
0 |
- |
9.89458 e-19 |
2.51065E-17 |
-25.78431373 |
chr13_19315890_19316198 |
chr13 |
3. |
ZNF965 | LINC00417 | CYP4F34 |
8.90044 e-14 |
1.19079 e-12 |
-25.87364383 |
chr18_61669993_61670289 |
chr18 |
1 |
SERPINB8 |
8.41432 e - 63 |
2.5838E-60 |
-26.04262437 |
chr20_32885922_32886673 |
chr20 |
1 |
阿西 |
2.8332E-44 |
4.47838 e-42 |
-26.45197851 |
chr6_106252261_106252558 |
chr6 |
0 |
- |
6.2211E-107 |
4.9875 e - 104 |
-26.54101932 |
chr2_2538383849_25384399 |
chr2 |
3. |
EFR3B | rp11 - 509 e16天| POMC |
4.25503E-85 |
2.26062 e - 82 |
-26.70759651 |
chr4_131633369_131633569 |
chr4 |
0 |
- |
1.21778E-09 |
8.14225 e-09 |
-26.8218303 |
chr4_26789871_26790007 |
chr4 |
0 |
- |
9.76527 e-06 |
2.75795 e-05 |
-27.15229384 |
chr1_5537080_55370265 |
chr1 |
0 |
- |
1.33489E-60 |
3.89366 e-58 |
-27.2302102 |
chr19_45619267_45619497 |
chr19 |
2 |
标记4 | PPP1R37 |
3.61011 e-48 |
6.62101E-46 |
-27.29034787 |
chr16_33588844_33589010 |
chr16 |
1 |
ENPP7P13 |
8.03476 e-26 |
4.0933E-24 |
-27.38040136 |
chr4_15907926_15908145 |
chr4 |
0 |
- |
2.8442 e-50 |
5.76083E-48 |
-27.44818039 |
chr10_67155111_67155236 |
chr10 |
0 |
- |
4.83108 e-11 |
4.17264E-10 |
-27.80333564 |
chr17_4278292_4278786 |
chr17 |
1 |
UBE2G1 |
9.00939 e-24 |
3.82074 e-22 |
-27.82640422 |
chr11_11634408_116344147 |
chr11 |
0 |
- |
0.000326633 |
0.000615342 |
-27.8388828 |
chr19_34245878_34246069 |
chr19 |
1 |
CHST8 |
6.69284 e-06 |
1.96741E-05 |
-27.92649973 |
chr17_16864290_16864524 |
chr17 |
1 |
TNFRSF13B |
1.26001 e-12 |
1.41214 e-11 |
-28.2842299 |
chr11\u 82354426\u 82354705 |
chr11 |
2 |
MIR4300HG | rp11 - 179系。 |
6.09835 e-07 |
2.30172E-06 |
-29.18358119 |
chr5_153676389_153676633 |
chr5 |
1 |
GALNT10 |
1.43406 e - 68 |
5.14737 e - 66 |
-29.70725527 |
chr10_134778418_134779164 |
chr10 |
3. |
LINC01166 | LINC01167 | LINC01168 |
5.1864E-178 |
1.2399E-174 |
-29.73911375 |
chr8_36995835_36995986 |
chr8 |
1 |
MIR1268A |
3.40507 e-09 |
2.0846E-08 |
-29.75107115 |
chr2_213316451_213316721 |
chr2 |
1 |
ERBB4 |
3.25312 e-05 |
8.05895 e-05 |
-30.06050559 |
chr3_105601223_105601548 |
chr3 |
0 |
- |
3.99011 e-26 |
2.08106 e-24 |
-30.45696192 |
chr2_130693963_130694229 |
chr2 |
3. |
图9P1 | LINC01856 | AC079776。 |
1.8989 e - 114 |
1.6726 e - 111 |
-30.54653298 |
chr11_110986763_110986975 |
chr11 |
1 |
RP11-89C3。 |
0 |
0 |
-30.61868687 |
chr4_184296182_184296485 |
chr4 |
2 |
RP11-451F20.| AC093844。 |
3.2812 e - 82 |
1.64531 e - 79 |
-30.6235367 |
chr6_21452696_21452935 |
chr6 |
0 |
- |
4.66098E-09 |
2.77827 e-08 |
-30.7652865 |
chr14_56669107_56669307 |
chr14 |
1 |
PELI2 |
0.005344129 |
0.006946025 |
-31.10639369 |
chr13_25141770_2514291 |
chr13 |
3. |
TPTE2P6 | PSPC1P | RP11-556N21。 |
2.11697 e-25 |
1.04092 e-23 |
-31.10709988 |
chr2_238796929_238797268 |
chr2 |
1 |
匝道1 |
9.04001 e-24 |
3.83251 e-22 |
-31.35072812 |
chr17_6901611_6901751 |
chr17 |
4 |
ALOX12-AS1 | rp11 - 589 p10。| rp11 - 589 p10。| ALOX12 |
0.00014541 |
0.000302279 |
-31.60823695 |
chr15_79299672_79299707 |
chr15 |
1 |
RASGRF1 |
0.004476538 |
0.005967375 |
-32.72230999 |
chr1_223353214_223353363 |
chr1 |
1 |
RP11-239E10 |
7.13359 e-18 |
1.64468E-16 |
-33.00889209 |
chr1_113221602_113221746 |
chr1 |
2 |
CAPZA1 | MOV10 |
8.44636 e-34 |
7.62526 e-32 |
-33.03827068 |
chr19_21860552_21861267 |
chr19 |
1 |
rp11 - 420 k14。 |
1.3469E-284 |
1.127E-280 |
-33.08420719 |
chr2_145505959_145506291 |
chr2 |
2 |
TEX41 | AC023128。 |
2.36911E-23 |
9.63501 e-22 |
-33.13077409 |
chr21_29565178_29565285 |
chr21 |
1 |
LINC01695 |
0.000196292 |
0.000393653 |
-33.4915241 |
chr22_47442504_47442671 |
chr22 |
1 |
TBC1D22A |
2.44869E-31 |
1.87658E-29 |
-34.87001855 |
chr8_119449323_119449547 |
chr8 |
1 |
SAMD12 |
2.1869 e-06 |
7.23312 e-06 |
-36.3138769 |
chr3_6706652_6706860 |
chr3 |
2 |
AC069277.| GRM7-AS3 |
0.00028562 |
0.000547251 |
-39.63810451 |
chr8_129286309_129286584 |
chr8 |
0 |
- |
3.30084 e-09 |
2.02608 e-08 |
-39.75752508 |
chr12_64067778_64067878 |
chr12 |
3. |
MIR548Z | DPY19L2 | rp11 - 415 i12。 |
0.000389652 |
0.000718873 |
-40.8170893 |
CHR157118771771187868 |
chr15 |
2 |
LRRC49 | THAP10 |
0.004522921 |
0.006020138 |
-42.45762712 |
chr3_115099771_115100023 |
chr3 |
0 |
- |
0.002555418 |
0.003683188 |
-42.60471914 |
chr17_57187586_57187924 |
chr17 |
3. |
TRIM37 | AC099850。| SKA2 |
2.39899 e-60 |
6.93704 e-58 |
-46.21784352 |