Autosomal sex-associated co-methylated regions predict biological sex from DNA methylation.
Autosomal sex-associated co-methylated regions predict biological sex from DNA methylation.
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DOI：
10.1093/nar/gkab682
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发表时间：
2021-09-20
影响因子：
14.9
通讯作者：
Aristizabal MJ
中科院分区：
文献类型：
--
作者：
Gatev E;Inkster AM;Negri GL;Konwar C;Lussier AA;Skakkebaek A;Sokolowski MB;Gravholt CH;Dunn EC;Kobor MS;Aristizabal MJ
性是一种健康调节器，在生物医学研究中一直被忽视。认识到这一知识差距后，资助机构现在要求将性别作为一个生物学变量纳入研究，目的是激励人们努力阐明健康和疾病中性别偏见的分子基础。DNA甲基化（DNAm）是介导这种性别偏见的强有力的分子候选；然而，对dna中性别差异的一种强有力的、很好表征的注释尚未出现。从一个来自标准成人全血样本的大型（n = 3795） dna图谱数据集开始，我们鉴定、验证并表征了常染色体性别相关的共甲基化基因组区域（sCMRs）。引人注目的是，sCMRs在整个生命过程中显示出一致的dna性别差异，并且一个子集在细胞、组织和癌症类型中也是一致的。scmr包括dna中已知存在性别差异的位点，以及与存在性别偏见影响的健康状况相关的位点。sCMRs的稳健性使常染色体dna预测性别的准确度达到96%。对性染色体非整倍体（Klinefelter [47,XXY], Turner [45，X]和47，XXX综合征）患者的血液DNAm谱进行测试，发现性染色体与性别偏性常染色体DNAm之间存在密切关系。
Sex is a modulator of health that has been historically overlooked in biomedical research. Recognizing this knowledge gap, funding agencies now mandate the inclusion of sex as a biological variable with the goal of stimulating efforts to illuminate the molecular underpinnings of sex biases in health and disease. DNA methylation (DNAm) is a strong molecular candidate for mediating such sex biases; however, a robust and well characterized annotation of sex differences in DNAm is yet to emerge. Beginning with a large (n = 3795) dataset of DNAm profiles from normative adult whole blood samples, we identified, validated and characterized autosomal sex-associated co-methylated genomic regions (sCMRs). Strikingly, sCMRs showed consistent sex differences in DNAm over the life course and a subset were also consistent across cell, tissue and cancer types. sCMRs included sites with known sex differences in DNAm and links to health conditions with sex biased effects. The robustness of sCMRs enabled the generation of an autosomal DNAm-based predictor of sex with 96% accuracy. Testing this tool on blood DNAm profiles from individuals with sex chromosome aneuploidies (Klinefelter [47,XXY], Turner [45,X] and 47,XXX syndrome) revealed an intimate relationship between sex chromosomes and sex-biased autosomal DNAm.
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影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
DOI：
10.1073/pnas.1820838116
发表时间：
2020-09-22
影响因子：
11.1
作者：
Aristizabal, Maria J.;Anreiter, Ina;O'Donnell, Kieran J.
通讯作者：
O'Donnell, Kieran J.
影响因子：
5.4
作者：
Gershoni M;Pietrokovski S
通讯作者：
Pietrokovski S
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
12.3
作者：
Gaunt TR;Shihab HA;Hemani G;Min JL;Woodward G;Lyttleton O;Zheng J;Duggirala A;McArdle WL;Ho K;Ring SM;Evans DM;Davey Smith G;Relton CL
通讯作者：
Relton CL