TY - JOUR
T1 - Genome-wide DNA methylation association study of recent and cumulative marijuana use in middle aged adults
AU - Nannini, Drew R.
AU - Zheng, Yinan
AU - Joyce, Brian T.
AU - Kim, Kyeezu
AU - Gao, Tao
AU - Wang, Jun
AU - Jacobs, David R.
AU - Schreiner, Pamela J.
AU - Yaffe, Kristine
AU - Greenland, Philip
AU - Lloyd-Jones, Donald M.
AU - Hou, Lifang
N1 - Funding Information:
The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Kaiser Foundation Research Institute (HHSN268201800004I), Northwestern University (HHSN268201800003I), the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), and the University of Minnesota (HHSN268201800006I). The DNA methylation laboratory and analytical work were funded by American Heart Association (14SFRN20790000 & 17SFRN33700278, Northwestern University) and National Institute on Aging (R21AG063370, R21AG068955, R01AG081244, and R01AG069120).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 (n = 1023), we observed 22 and 31 methylation markers associated (FDR P ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 (n = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis-meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.
AB - Marijuana is a widely used psychoactive substance in the US and medical and recreational legalization has risen over the past decade. Despite the growing number of individuals using marijuana, studies investigating the association between epigenetic factors and recent and cumulative marijuana use remain limited. We therefore investigated the association between recent and cumulative marijuana use and DNA methylation levels. Participants from the Coronary Artery Risk Development in Young Adults Study with whole blood collected at examination years (Y) 15 and Y20 were randomly selected to undergo DNA methylation profiling at both timepoints using the Illumina MethylationEPIC BeadChip. Recent use of marijuana was queried at each examination and used to estimate cumulative marijuana use from Y0 to Y15 and Y20. At Y15 (n = 1023), we observed 22 and 31 methylation markers associated (FDR P ≤ 0.05) with recent and cumulative marijuana use and 132 and 16 methylation markers at Y20 (n = 883), respectively. We replicated 8 previously reported methylation markers associated with marijuana use. We further identified 640 cis-meQTLs and 198 DMRs associated with recent and cumulative use at Y15 and Y20. Differentially methylated genes were statistically overrepresented in pathways relating to cellular proliferation, hormone signaling, and infections as well as schizophrenia, bipolar disorder, and substance-related disorders. We identified numerous methylation markers, pathways, and diseases associated with recent and cumulative marijuana use in middle-aged adults, providing additional insight into the association between marijuana use and the epigenome. These results provide novel insights into the role marijuana has on the epigenome and related health conditions.
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U2 - 10.1038/s41380-023-02106-y
DO - 10.1038/s41380-023-02106-y
M3 - Article
C2 - 37258616
AN - SCOPUS:85160774517
SN - 1359-4184
JO - Molecular Psychiatry
JF - Molecular Psychiatry
ER -