Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction

BMC Genomics

Research Article

David C. Qian¹  Yafang Li¹  Maxime Vaissié¹  Christopher I. Amos¹  Alexander J. Titus²  Ralf Krahe³  Jennifer L. Jin⁴  Yixuan He⁵  Humsini Viswanath⁶  Philip R. Baldwin⁷  Ramiro Salas⁷  David L. Molfese⁷ 

[1] Department of Biomedical Data Science, Dartmouth Geisel School of Medicine, 03756, Lebanon, NH, USA;Department of Epidemiology, Dartmouth Geisel School of Medicine, 03756, Lebanon, NH, USA;Department of Genetics, University of Texas MD Anderson Cancer Center, 77030, Houston, TX, USA;Department of Mathematics, Dartmouth College, 03755, Hanover, NH, USA;Department of Mathematics, Dartmouth College, 03755, Hanover, NH, USA;Department of Biological Sciences, Dartmouth College, 03755, Hanover, NH, USA;Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 77030, Houston, TX, USA;Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, 77030, Houston, TX, USA;Michael E. DeBakey Veterans Affairs Medical Center, 77030, Houston, TX, USA;

关键词: Functional magnetic resonance imaging;    Genome-wide association studies;    Smoking addiction;    Caudate activity;    Gene set enrichment analysis;   

DOI  :  10.1186/s12864-017-4124-5

 received in 2017-01-29, accepted in 2017-09-06,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNearly 6 million deaths and over a half trillion dollars in healthcare costs worldwide are attributed to tobacco smoking each year. Extensive research efforts have been pursued to elucidate the molecular underpinnings of smoking addiction and facilitate cessation. In this study, we genotyped and obtained both resting state and task-based functional magnetic resonance imaging from 64 non-smokers and 42 smokers. Smokers were imaged after having smoked normally (“sated”) and after having not smoked for at least 12 h (“abstinent”).ResultsWhile abstinent smokers did not differ from non-smokers with respect to pairwise resting state functional connectivities (RSFCs) between 12 brain regions of interest, RSFCs involving the caudate and putamen of sated smokers significantly differed from those of non-smokers (P < 0.01). Further analyses of caudate and putamen activity during elicited experiences of reward and disappointment show that caudate activity during reward (CR) correlated with smoking status (P = 0.015). Moreover, abstinent smokers with lower CR experienced greater withdrawal symptoms (P = 0.024), which suggests CR may be related to smoking urges. Associations between genetic variants and CR, adjusted for smoking status, were identified by genome-wide association study (GWAS). Genes containing or exhibiting caudate-specific expression regulation by these variants were enriched within Gene Ontology terms that describe cytoskeleton functions, synaptic organization, and injury response (P < 0.001, FDR < 0.05).ConclusionsBy integrating genomic and imaging data, novel insights into potential mechanisms of caudate activation and homeostasis are revealed that may guide new directions of research toward improving our understanding of addiction pathology.

【 授权许可】

CC BY   
© The Author(s). 2017