期刊
HUMAN BRAIN MAPPING
卷 36, 期 8, 页码 3007-3019出版社
WILEY
DOI: 10.1002/hbm.22824
关键词
alcohol use disorder; single nucleotide polymorphism; functional magnetic resonance imaging; parallel independent component analysis with multiple references; precuneus; cAMP-response element-binding; brain derived neurotrophic factor
资金
- National Institutes of Health [R33DA027626, P20GM103472, R01EB006841, R01EB005846, R01AA012238]
Alcohol use disorder (AUD) is suggested to have polygenic risk factors and also exhibits neurological complications, strongly encouraging a translational study to explore the associations between aggregates of genetic variants and brain function alterations related to alcohol use. In this study, we used a semiblind multivariate approach, parallel independent component analysis with multiple references (pICA-MR) to investigate relationships of genome-wide single nucleotide polymorphisms with alcohol cue-elicited brain activations in 315 heavy drinkers, where pICA-MR assesses multiple reference genes for their architecture and functional influences on neurobiological conditions. The genetic component derived from the cAMP-response element-binding protein and -brain derived neurotrophic factor (CREB-BDNF) pathway reference was significantly associated (r=-0.38, P=3.98 x 10(-12)) with an imaging component reflecting hyperactivation in precuneus, superior parietal lobule, and posterior cingulate for drinkers with more severe alcohol dependence symptoms. The highlighted brain regions participate in many cognitive processes and have been robustly implicated in craving-related studies. The genetic factor highlighted the CREB and BDNF references, as well as other genes including GRM5, GRM7, GRID1, GRIN2A, PRKCA, and PRKCB. Ingenuity Pathway Analysis indicated that the genetic component was enriched in synaptic plasticity, GABA, and protein kinase A signaling. Collectively, our findings suggest that genetic variations in various neural plasticity and signaling pathways partially explain the variance of precuneus reactivity to alcohol cues which appears to be associated with AUD severity. Hum Brain Mapp 36:3007-3019, 2015. (c) 2015 Wiley Periodicals, Inc.
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