Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome.
Differentially expressed genes reflect disease-induced rather than disease-causing changes in the transcriptome.
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差异表达的基因反映了转录组中疾病诱导的而不是致病的变化。
DOI：
10.1038/s41467-021-25805-y
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发表时间：
2021-09-24
影响因子：
16.6
通讯作者：
Kutalik Z
中科院分区：
文献类型：
--
作者：
Porcu E;Sadler MC;Lepik K;Auwerx C;Wood AR;Weihs A;Sleiman MSB;Ribeiro DM;Bandinelli S;Tanaka T;Nauck M;Völker U;Delaneau O;Metspalu A;Teumer A;Frayling T;Santoni FA;Reymond A;Kutalik Z
比较健康和患病个体之间的转录水平允许鉴定差异表达的基因，其可能是所审查的疾病的原因、后果或仅仅相关。我们提出了一种方法来分解观察基因表达和表型之间的相关性驱动的混杂因素，正向和反向因果效应。基因表达和复杂性状之间的双向因果效应通过孟德尔随机化整合来自GWAS和全血eQTL的汇总水平数据获得。将这种方法应用于复杂性状表明，前向效应的贡献可以忽略不计。例如，BMI-基因表达相关系数与性状-基因表达因果效应（rBMI = 0.11，PBMI = 2.0 × 10−51和rTG = 0.13，PTG = 1.1 × 10−68）之间存在显著相关性，但与基因表达-性状效应之间的相关性不可检测。我们的研究结果表明，比较患病和健康受试者的转录组的研究更容易揭示疾病诱导的基因表达变化，而不是致病的。识别健康和患病个体之间的基因表达变化可以揭示机制见解和生物标志物。在这里，作者提出了一种双向转录组范围的孟德尔随机化方法来评估基因表达和复杂性状之间的因果关系。
Comparing transcript levels between healthy and diseased individuals allows the identification of differentially expressed genes, which may be causes, consequences or mere correlates of the disease under scrutiny. We propose a method to decompose the observational correlation between gene expression and phenotypes driven by confounders, forward- and reverse causal effects. The bi-directional causal effects between gene expression and complex traits are obtained by Mendelian Randomization integrating summary-level data from GWAS and whole-blood eQTLs. Applying this approach to complex traits reveals that forward effects have negligible contribution. For example, BMI- and triglycerides-gene expression correlation coefficients robustly correlate with trait-to-expression causal effects (rBMI = 0.11, PBMI = 2.0 × 10−51 and rTG = 0.13, PTG = 1.1 × 10−68), but not detectably with expression-to-trait effects. Our results demonstrate that studies comparing the transcriptome of diseased and healthy subjects are more prone to reveal disease-induced gene expression changes rather than disease causing ones. Identification of gene expression changes between healthy and diseased individuals can reveal mechanistic insights and biomarkers. Here, the authors propose a bi-directional transcriptome-wide Mendelian Randomization approach to assess causal effects between gene expression and complex traits.
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影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
DOI：
10.1111/j.1532-5415.2000.tb03873.x
发表时间：
2000-12-01
影响因子：
6.3
作者：
Ferrucci, L;Bandinelli, S;Guralnik, JM
通讯作者：
Guralnik, JM
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.