Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences.
Methylomic Investigation of Problematic Adolescent Cannabis Use and Its Negative Mental Health Consequences.
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DOI：
10.1016/j.jaac.2021.02.008
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发表时间：
2021-12
影响因子：
13.3
通讯作者：
van den Oord EJCG
中科院分区：
文献类型：
--
作者：
Clark SL;Chan R;Zhao M;Xie LY;Copeland WE;Aberg KA;van den Oord EJCG
青少年吸食大麻的影响是一个紧迫的公共卫生问题，因为吸食大麻的比率很高，而且与不良后果有关联。在这里，我们考虑了问题青少年大麻使用和甲基化之间的联系。使用基于浓缩的测序方法，我们对来自大烟山研究的703个青少年样本进行了一项有问题的青少年大麻使用的甲基组范围关联研究(MWAS)。利用表观基因组去卷积技术，我们对血液中的主要细胞类型：粒细胞、T细胞、B细胞和单核细胞进行了MWASS。进行了浓缩测试，以确定与大麻相关的甲基化差异和与青少年使用大麻的负面心理健康影响有关的变异之间的重叠。全血鉴定出45个显著的CPG，而细胞类型特异性分析产生了全血MWA中没有鉴定的另外32个CPG。我们观察到B细胞MWAs和教育程度和智力的基因研究之间有显著的重叠。此外，来自T细胞和单核细胞的结果与在脑组织中进行的精神疾病的多学科研究的结果重叠。在对青少年大麻使用进行的第一批全基因组研究之一中，我们确定了位于潜在相关大脑功能重要基因中的几个甲基化位点。我们的发现导致了几个可测试的假说，通过这些假说，大麻相关的甲基化可以影响神经发育、炎症反应，以及将大麻相关的甲基化与潜在的下游心理健康影响联系起来的潜在机制。
The impact of adolescent cannabis use is a pressing public health question due to the high rates of use and links to negative outcomes. Here we consider the association between problematic adolescent cannabis use and methylation. Using an enrichment-based sequencing approach, we performed a methylome-wide association study (MWAS) of problematic adolescent cannabis use in 703 adolescent samples from the Great Smoky Mountain Study. Using epigenomic deconvolution, we performed MWASs for the main cell types in blood: granulocytes, T-cells, B-cells and monocytes. Enrichment testing was conducted to establish overlap between cannabis-associated methylation differences and variants associated with negative mental health effects of adolescent cannabis use. Whole blood identified 45 significant CpGs, and cell-type specific analyses yielded 32 additional CpGs not identified in the whole blood MWAS. We observed significant overlap between the B-cell MWAS and genetic studies of education attainment and intelligence. Furthermore, the results from both T-cells and monocytes overlapped with findings from a MWAS of psychosis conducted in brain tissue. In one of the first methylome-wide studies of adolescent cannabis use, we identified several methylation sites located in genes of importance for potentially relevant brain functions. Our findings resulted in several testable hypotheses by which cannabis-associated methylation can impact neurological development, inflammation response, as well as potential mechanisms linking cannabis-associated methylation to potential downstream mental health effects.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
6.8
作者：
Gerra MC;Jayanthi S;Manfredini M;Walther D;Schroeder J;Phillips KA;Cadet JL;Donnini C
通讯作者：
Donnini C
影响因子：
3.5
作者：
Gowran, Aoife;Murphy, Carrie E.;Campbell, Veronica A.
通讯作者：
Campbell, Veronica A.
DOI：
10.1016/j.bbalip.2018.02.001
发表时间：
2018-05
期刊：
Biochimica et biophysica acta. Molecular and cell biology of lipids
影响因子：
--
作者：
Leishman E;Murphy M;Mackie K;Bradshaw HB
通讯作者：
Bradshaw HB
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GALIEGUE, S;MARY, S;CASELLAS, P
通讯作者：
CASELLAS, P