Leveraging DNA-Methylation Quantitative-Trait Loci to Characterize the Relationship between Methylomic Variation, Gene Expression, and Complex Traits.
Leveraging DNA-Methylation Quantitative-Trait Loci to Characterize the Relationship between Methylomic Variation, Gene Expression, and Complex Traits.
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DOI：
10.1016/j.ajhg.2018.09.007
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发表时间：
2018-11-01
影响因子：
9.8
通讯作者：
Mill J
中科院分区：
文献类型：
--
作者：
Hannon E;Gorrie-Stone TJ;Smart MC;Burrage J;Hughes A;Bao Y;Kumari M;Schalkwyk LC;Mill J
表征遗传、表观遗传和转录组变异之间的复杂关系有可能增进对健康和疾病表型基础机制的理解。我们使用 Illumina EPIC 阵列对英国家庭纵向研究的样本进行分析，对 DNA 甲基化 (DNAm) 的常见遗传变异进行了全面分析。我们确定了 2,907,234 个遗传变异和 93,268 个 DNAm 位点之间发生的 12,689,548 个显着 DNA 甲基化数量性状位点 (mQTL) 关联 (p < 6.52 × 10−14)，其中包括大量以前的 DNAm 分析方法未识别的数量。我们通过使用基于汇总数据的孟德尔随机化 (SMR) 来识别 36 个复杂性状和 1,246 个 DNAm 位点之间的 1,662 个多效性关联，证明了这些数据在解释与超过 60 个人类性状相关的常见遗传变异的功能后果方面的实用性。我们还使用 SMR 来表征 DNAm 和基因表达之间的关系，从而识别 5,420 个 DNAm 位点和 1,702 个基因的转录之间的 6,798 个多效关联。我们的 mQTL 数据库和 SMR 结果可通过可搜索的在线数据库作为研究界的资源获得。
Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation has the potential to increase understanding about the mechanisms underpinning health and disease phenotypes. We undertook a comprehensive analysis of common genetic variation on DNA methylation (DNAm) by using the Illumina EPIC array to profile samples from the UK Household Longitudinal study. We identified 12,689,548 significant DNA methylation quantitative trait loci (mQTL) associations (p < 6.52 × 10−14) occurring between 2,907,234 genetic variants and 93,268 DNAm sites, including a large number not identified by previous DNAm-profiling methods. We demonstrate the utility of these data for interpreting the functional consequences of common genetic variation associated with > 60 human traits by using summary-data-based Mendelian randomization (SMR) to identify 1,662 pleiotropic associations between 36 complex traits and 1,246 DNAm sites. We also use SMR to characterize the relationship between DNAm and gene expression and thereby identify 6,798 pleiotropic associations between 5,420 DNAm sites and the transcription of 1,702 genes. Our mQTL database and SMR results are available via a searchable online database as a resource to the research community.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
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Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
7.7
作者：
Gutierrez-Arcelus M;Lappalainen T;Montgomery SB;Buil A;Ongen H;Yurovsky A;Bryois J;Giger T;Romano L;Planchon A;Falconnet E;Bielser D;Gagnebin M;Padioleau I;Borel C;Letourneau A;Makrythanasis P;Guipponi M;Gehrig C;Antonarakis SE;Dermitzakis ET
通讯作者：
Dermitzakis ET
影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
9.8
作者：
Hannon E;Weedon M;Bray N;O'Donovan M;Mill J
通讯作者：
Mill J