PMID- 38422867
OWN - NLM
STAT- MEDLINE
DCOM- 20240319
LR  - 20240425
IS  - 1872-7123 (Electronic)
IS  - 0165-1781 (Print)
IS  - 0165-1781 (Linking)
VI  - 334
DP  - 2024 Apr
TI  - Neurogenetic underpinnings of nicotine use severity: Integrating the brain 
      transcriptomes and GWAS variants via network approaches.
PG  - 115815
LID - S0165-1781(24)00100-8 [pii]
LID - 10.1016/j.psychres.2024.115815 [doi]
AB  - Our study focused on human brain transcriptomes and the genetic risks of 
      cigarettes per day (CPD) to investigate the neurogenetic mechanisms of individual 
      variation in nicotine use severity. We constructed whole-brain and intramodular 
      region-specific coexpression networks using BrainSpan's transcriptomes, and the 
      genomewide association studies identified risk variants of CPD, confirmed the 
      associations between CPD and each gene set in the region-specific subnetworks 
      using an independent dataset, and conducted bioinformatic analyses. Eight 
      brain-region-specific coexpression subnetworks were identified in association 
      with CPD: amygdala, hippocampus, medial prefrontal cortex (MPFC), orbitofrontal 
      cortex (OPFC), dorsolateral prefrontal cortex, striatum, mediodorsal nucleus of 
      the thalamus (MDTHAL), and primary motor cortex (M1C). Each gene set in the eight 
      subnetworks was associated with CPD. We also identified three hub proteins 
      encoded by GRIN2A in the amygdala, PMCA2 in the hippocampus, MPFC, OPFC, 
      striatum, and MDTHAL, and SV2B in M1C. Intriguingly, the pancreatic secretion 
      pathway appeared in all the significant protein interaction subnetworks, 
      suggesting pleiotropic effects between cigarette smoking and pancreatic diseases. 
      The three hub proteins and genes are implicated in stress response, drug memory, 
      calcium homeostasis, and inhibitory control. These findings provide novel 
      evidence of the neurogenetic underpinnings of smoking severity.
CI  - Copyright (c) 2024 Elsevier B.V. All rights reserved.
FAU - Yang, Bao-Zhu
AU  - Yang BZ
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 
      Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA. Electronic 
      address: bao-zhu.yang@yale.edu.
FAU - Xiang, Bo
AU  - Xiang B
AD  - Department of Psychiatry, Affiliated Hospital of Southwest Medical University, 
      Luzhou, Sichuan Province, China. Electronic address: xiangbo@swmu.edu.cn.
FAU - Wang, Tingting
AU  - Wang T
AD  - Department of Psychiatry, Affiliated Hospital of Southwest Medical University, 
      Luzhou, Sichuan Province, China.
FAU - Ma, Shuangge
AU  - Ma S
AD  - Department of Biostatistics, Yale University, New Haven, CT, USA.
FAU - Li, Chiang-Shan R
AU  - Li CR
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA; 
      Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 
      USA; Wu Tsai Institute, Yale University, New Haven, CT, USA.
LA  - eng
GR  - R01 DA051922/DA/NIDA NIH HHS/United States
GR  - R03 DA047562/DA/NIDA NIH HHS/United States
GR  - R21 CA252916/CA/NCI NIH HHS/United States
GR  - R21 DA045189/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20240228
PL  - Ireland
TA  - Psychiatry Res
JT  - Psychiatry research
JID - 7911385
RN  - 6M3C89ZY6R (Nicotine)
SB  - IM
MH  - Humans
MH  - *Nicotine
MH  - *Genome-Wide Association Study
MH  - Transcriptome
MH  - Brain
MH  - Corpus Striatum
PMC - PMC11017751
MID - NIHMS1971249
OTO - NOTNLM
OT  - Brain transcriptome
OT  - Cigarettes per day
OT  - Coexpression network
OT  - GRIN2A
OT  - PMCA2
OT  - SV2B
COIS- Declaration of competing interest None.
EDAT- 2024/03/01 01:22
MHDA- 2024/03/19 06:44
PMCR- 2025/04/01
CRDT- 2024/02/29 18:13
PHST- 2024/01/02 00:00 [received]
PHST- 2024/02/19 00:00 [revised]
PHST- 2024/02/23 00:00 [accepted]
PHST- 2025/04/01 00:00 [pmc-release]
PHST- 2024/03/19 06:44 [medline]
PHST- 2024/03/01 01:22 [pubmed]
PHST- 2024/02/29 18:13 [entrez]
AID - S0165-1781(24)00100-8 [pii]
AID - 10.1016/j.psychres.2024.115815 [doi]
PST - ppublish
SO  - Psychiatry Res. 2024 Apr;334:115815. doi: 10.1016/j.psychres.2024.115815. Epub 
      2024 Feb 28.