Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction
Abstract Background Nearly 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,...
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doaj-bbda8a22707a4fad9f35e2a12d1f38372020-11-24T22:17:54ZengBMCBMC Genomics1471-21642017-09-0118111010.1186/s12864-017-4124-5Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addictionDavid C. Qian0David L. Molfese1Jennifer L. Jin2Alexander J. Titus3Yixuan He4Yafang Li5Maxime Vaissié6Humsini Viswanath7Philip R. Baldwin8Ralf Krahe9Ramiro Salas10Christopher I. Amos11Department of Biomedical Data Science, Dartmouth Geisel School of MedicineMenninger Department of Psychiatry and Behavioral SciencesDepartment of Mathematics, Dartmouth CollegeDepartment of Epidemiology, Dartmouth Geisel School of MedicineDepartment of Mathematics, Dartmouth CollegeDepartment of Biomedical Data Science, Dartmouth Geisel School of MedicineDepartment of Biomedical Data Science, Dartmouth Geisel School of MedicineMenninger Department of Psychiatry and Behavioral SciencesMenninger Department of Psychiatry and Behavioral SciencesDepartment of Genetics, University of Texas MD Anderson Cancer CenterMenninger Department of Psychiatry and Behavioral SciencesDepartment of Biomedical Data Science, Dartmouth Geisel School of MedicineAbstract Background Nearly 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”). Results While 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). Conclusions By 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.http://link.springer.com/article/10.1186/s12864-017-4124-5Functional magnetic resonance imagingGenome-wide association studiesSmoking addictionCaudate activityGene set enrichment analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David C. Qian David L. Molfese Jennifer L. Jin Alexander J. Titus Yixuan He Yafang Li Maxime Vaissié Humsini Viswanath Philip R. Baldwin Ralf Krahe Ramiro Salas Christopher I. Amos |
spellingShingle |
David C. Qian David L. Molfese Jennifer L. Jin Alexander J. Titus Yixuan He Yafang Li Maxime Vaissié Humsini Viswanath Philip R. Baldwin Ralf Krahe Ramiro Salas Christopher I. Amos Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction BMC Genomics Functional magnetic resonance imaging Genome-wide association studies Smoking addiction Caudate activity Gene set enrichment analysis |
author_facet |
David C. Qian David L. Molfese Jennifer L. Jin Alexander J. Titus Yixuan He Yafang Li Maxime Vaissié Humsini Viswanath Philip R. Baldwin Ralf Krahe Ramiro Salas Christopher I. Amos |
author_sort |
David C. Qian |
title |
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
title_short |
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
title_full |
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
title_fullStr |
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
title_full_unstemmed |
Genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
title_sort |
genome-wide imaging association study implicates functional activity and glial homeostasis of the caudate in smoking addiction |
publisher |
BMC |
series |
BMC Genomics |
issn |
1471-2164 |
publishDate |
2017-09-01 |
description |
Abstract Background Nearly 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”). Results While 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). Conclusions By 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. |
topic |
Functional magnetic resonance imaging Genome-wide association studies Smoking addiction Caudate activity Gene set enrichment analysis |
url |
http://link.springer.com/article/10.1186/s12864-017-4124-5 |
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