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Christopher P King, Apurva S Chitre, Joel D Leal-Gutiérrez, Jordan A Tripi, Alesa R Hughson, Aidan P Horvath, Alexander C Lamparelli, Anthony George, Connor Martin, Celine L St Pierre, Hannah V Bimschleger, Jianjun Gao, Riyan Cheng, Khai-Minh Nguyen, Katie L Holl, Oksana Polesskaya, Keita Ishiwari, Hao Chen, Leah C Solberg Woods, Abraham A Palmer, Terry E Robinson, Shelly B Flagel, Paul J Meyer
Addiction vulnerability is associated with the tendency to attribute incentive salience to reward predictive cues; both addiction and the attribution of incentive salience are influenced by environmental and genetic factors. To characterize the genetic contributions to incentive salience attribution, we performed a genome-wide association study (GWAS) in a cohort of 1,645 genetically diverse heterogeneous stock (HS) rats. We tested HS rats in a Pavlovian conditioned approach task, in which we characterized the individual responses to food-associated stimuli ("cues")...
March 14, 2024: bioRxiv
#2
JOURNAL ARTICLE
Xiaoqiang Shi, Meng Li, Jianhua Yao, Ming D Li, Zhongli Yang
BACKGROUND AND AIMS: Whether alcohol-related DNA methylation has a causal effect on psychiatric disorders has not been investigated. Furthermore, a comprehensive investigation into the causal relationship and underlying mechanisms linking alcohol consumption and psychiatric disorders has been lacking. This study aimed to evaluate the causal effect of general alcohol intake and pathological drinking behaviors on psychiatric disorders, alcohol-associated DNA methylation on gene expression and psychiatric disorders, and gene expression on psychiatric disorders...
March 25, 2024: Addiction
#3
JOURNAL ARTICLE
Germán D Carrasquilla, Mario García-Ureña, María J Romero-Lado, Tuomas O Kilpeläinen
BACKGROUND AND AIMS: Smokers tend to have a lower body weight than non-smokers, but also more abdominal fat. It remains unclear whether or not the relationship between smoking and abdominal obesity is causal. Previous Mendelian randomization (MR) studies have investigated this relationship by relying upon a single genetic variant for smoking heaviness. This approach is sensitive to pleiotropic effects and may produce imprecise causal estimates. We aimed to estimate causality between smoking and abdominal obesity using multiple genetic instruments...
March 20, 2024: Addiction
#4
JOURNAL ARTICLE
Alex P Miller, Ian R Gizer
Sensation seeking is bidirectionally associated with levels of alcohol consumption in both adult and adolescent samples, and shared neurobiological and genetic influences may in part explain these associations. Links between sensation seeking and alcohol use disorder (AUD) may primarily manifest via increased alcohol consumption rather than through direct effects on increasing problems and consequences. Here the overlap among sensation seeking, alcohol consumption, and AUD was examined using multivariate modelling approaches for genome-wide association study (GWAS) summary statistics in conjunction with neurobiologically informed analyses at multiple levels of investigation...
February 2024: Addiction Biology
#5
JOURNAL ARTICLE
Jingsong Luo, Yuxin Chen, Yanmin Tao, Yaxin Xu, Kexin Yu, Oguz Anwar, Yueqi Zong, Yufei Chen, Tingting Deng
BACKGROUND: The popularity of digital devices seems to provide a new observational variable for early identification and prevention of suicide with the development of the information technology era. Nevertheless, whether it is the use of digital devices that alters suicide risk or suicide risk manifests itself through change digital device use needs to be further explored. METHODS: Bidirectional Mendelian randomization (MR) analysis was used to explore potential causal relationships in the perspective of genetic prediction...
January 18, 2024: Journal of Affective Disorders
#6
JOURNAL ARTICLE
Q Wu, D Yang, W Dong, Z Song, J Yang, Y Gu
PURPOSE: As the global population continues to age, there is a noticeable yearly rise in the incidence of hernias. Simultaneously, smoking, a widespread addictive behavior and a significant contributor to mortality, has evolved into a pervasive public health concern. Existing literature has already established a connection between smoking and an increased risk of postoperative recurrence and postoperative infections following hernia surgery. However, there remains a dearth of research exploring the association between smoking and hernia morbidity...
December 26, 2023: Hernia: the Journal of Hernias and Abdominal Wall Surgery
#7
JOURNAL ARTICLE
Hamdi Mbarek, Scott D Gordon, David L Duffy, Nikki Hubers, Sally Mortlock, Jeffrey J Beck, Jouke-Jan Hottenga, René Pool, Conor V Dolan, Ky'Era V Actkins, Zachary F Gerring, Jenny Van Dongen, Erik A Ehli, William G Iacono, Matt Mcgue, Daniel I Chasman, C Scott Gallagher, Samantha L P Schilit, Cynthia C Morton, Guillaume Paré, Gonneke Willemsen, David C Whiteman, Catherine M Olsen, Catherine Derom, Robert Vlietinck, Daniel Gudbjartsson, Lisa Cannon-Albright, Eva Krapohl, Robert Plomin, Patrik K E Magnusson, Nancy L Pedersen, Pirro Hysi, Massimo Mangino, Timothy D Spector, Teemu Palviainen, Yuri Milaneschi, Brenda W Penninnx, Adrian I Campos, Ken K Ong, John R B Perry, Cornelis B Lambalk, Jaakko Kaprio, Ísleifur Ólafsson, Karine Duroure, Céline Revenu, Miguel E Rentería, Loic Yengo, Lea Davis, Eske M Derks, Sarah E Medland, Hreinn Stefansson, Kari Stefansson, Filippo Del Bene, Bruno Reversade, Grant W Montgomery, Dorret I Boomsma, Nicholas G Martin
STUDY QUESTION: Which genetic factors regulate female propensity for giving birth to spontaneous dizygotic (DZ) twins? SUMMARY ANSWER: We identified four new loci, GNRH1, FSHR, ZFPM1, and IPO8, in addition to previously identified loci, FSHB and SMAD3. WHAT IS KNOWN ALREADY: The propensity to give birth to DZ twins runs in families. Earlier, we reported that FSHB and SMAD3 as associated with DZ twinning and female fertility measures. STUDY DESIGN, SIZE, DURATION: We conducted a genome-wide association meta-analysis (GWAMA) of mothers of spontaneous dizygotic (DZ) twins (8265 cases, 264 567 controls) and of independent DZ twin offspring (26 252 cases, 417 433 controls)...
December 5, 2023: Human Reproduction
#8
JOURNAL ARTICLE
Lea Zillich, Josephin Wagner, Rachel H McMahan, Lauren M Park, Colin Hodgkinson, Elizabeth J Kovacs, Falk W Lohoff
Excessive alcohol consumption has detrimental effects on the entire organism, especially on the liver. The toxicity is partly dependent on age, as older individuals metabolize alcohol more slowly leading to increased cellular injury. This study aimed to investigate the effects of moderate binge drinking on the liver of young and aged mice in a genome-wide multi-omics approach. We determined DNA methylation (DNAm) using the Illumina MouseMethylation array and gene expression by RNA sequencing in 18 female Balb/c mice in a 2 × 2 design...
December 2023: Addiction Biology
#9
JOURNAL ARTICLE
Ester Antón-Galindo, Judit Cabana-Domínguez, Bàrbara Torrico, Roser Corominas, Bru Cormand, Noèlia Fernàndez-Castillo
INTRODUCTION: Co-occurrence of substance use disorders (SUD) and other behavioral conditions, such as stress-related, aggressive or risk-taking behaviors, in the same individual has been frequently described. As dopamine (DA) and serotonin (5-HT) have been previously identified as key neurotransmitters for some of these phenotypes, we explored the genetic contribution of these pathways to SUD and these comorbid phenotypes in order to better understand the genetic relationship between them...
2023: Frontiers in Psychiatry
#10
JOURNAL ARTICLE
Kenneth Blum, Panayotis K Thanos, Colin Hanna, Mark S Gold, David Baron, Igor Elman
Since 1990, there have been thousands of published studies on addiction psychiatry. Several from Blum et al showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance abuse and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, reactions have been mixed...
2023: Psychology Research and Behavior Management
#11
JOURNAL ARTICLE
Yihong Zhao, Xuewei Han, Zhi-Liang Zheng
Substance use disorder (SUD) arises from the initiation to subsequent regular, irregular and harmful use of substances such as alcohol, tobacco/nicotine and cannabis. While thousands of genetic variants have been identified from recent large-scale genome-wide association studies (GWAS), understanding their functions in substance involvement and investigating the mechanisms by which they act in the addiction circuits remains challenging. In this study, we re-analysed the brain regional transcriptome data from the most comprehensive postmortem transcriptomic study, with a focus on up- or down-regulation of substance-associated protein-coding genes in the addiction circuit-related brain regions (AddictRegions), including six cortical and 11 subcortical regions...
October 2023: Addiction Biology
#12
JOURNAL ARTICLE
Chen Mo, Zhenyao Ye, Yezhi Pan, Yuan Zhang, Qiong Wu, Chuan Bi, Song Liu, Braxton Mitchell, Peter Kochunov, L Elliot Hong, Tianzhou Ma, Shuo Chen
In the last two decades of Genome-wide association studies (GWAS), nicotine-dependence-related genetic loci (e.g., nicotinic acetylcholine receptor - nAChR subunit genes) are among the most replicable genetic findings. Although GWAS results have reported tens of thousands of SNPs within these loci, further analysis (e.g., fine-mapping) is required to identify the causal variants. However, it is computationally challenging for existing fine-mapping methods to reliably identify causal variants from thousands of candidate SNPs based on the posterior inclusion probability...
August 25, 2023: Molecular and Cellular Neurosciences
#13
JOURNAL ARTICLE
Kenneth Blum, Abdala Bowirrat, Igor Elman, David Baron, Panayotis K Thanos, Mark S Gold, Colin Hanna, Milan T Makale, Keerthy Sunder, Nicole Jafari, Foojan Zeine, Kevin T Murphy, Miles Makale, Rajendra D Badgaiyan
Since 1990, published addiction psychiatry articles have exceeded 11,495. Several from Blum et al. showed the clinical relevance of the Genetic Addiction Risk Severity (GARS) test in identifying risk for reward deficiency behaviors in cohorts from polysubstance and pain clinics, post-surgical bariatrics, and DWI offenders facing prison time. Since Blum et al first published in JAMA (1990) concerning the association of the DRD2 gene polymorphism and severe alcoholism, confirmation has been mixed and controversial...
June 29, 2023: Clinical and Experimental Psychology
#14
JOURNAL ARTICLE
Laura A Greco, William R Reay, Christopher V Dayas, Murray J Cairns
Cannabis use disorder (CUD) remains a significant public health issue globally, affecting up to one in five adults who use cannabis. Despite extensive research into the molecular underpinnings of the condition, there are no effective pharmacological treatment options available. Therefore, we sought to further explore genetic analyses to prioritise opportunities to repurpose existing drugs for CUD. Specifically, we aimed to identify druggable genes associated with the disorder, integrate transcriptomic/proteomic data and estimate genetic relationships with clinically actionable biochemical traits...
August 2023: Addiction Biology
#15
JOURNAL ARTICLE
Arshad H Khan, Jared R Bagley, Nathan LaPierre, Carlos Gonzalez-Figueroa, Tadeo C Spencer, Mudra Choudhury, Xinshu Xiao, Eleazar Eskin, James D Jentsch, Desmond J Smith
To identify addiction genes, we evaluate intravenous self-administration of cocaine or saline in 84 inbred and recombinant inbred mouse strains over 10 days. We integrate the behavior data with brain RNA-seq data from 41 strains. The self-administration of cocaine and that of saline are genetically distinct. We maximize power to map loci for cocaine intake by using a linear mixed model to account for this longitudinal phenotype while correcting for population structure. A total of 15 unique significant loci are identified in the genome-wide association study...
July 22, 2023: Cell Reports
#16
JOURNAL ARTICLE
Eleonora Iob, Jean-Baptiste Pingault, Marcus R Munafò, Brendon Stubbs, Mark S Gilthorpe, Adam X Maihofer, Andrea Danese
Observational studies suggest that physical activity can reduce the risk of mental health and substance use disorders. However, it is unclear whether this relationship is causal or explained by confounding bias (e.g., common underlying causes or reverse causality). We investigated the bidirectional causal relationship of physical activity (PA) and sedentary behaviour (SB) with ten mental health and substance use disorders, applying two-sample Mendelian Randomisation (MR). Genetic instruments for the exposures and outcomes were derived from the largest available, non-overlapping genome-wide association studies (GWAS)...
July 21, 2023: Molecular Psychiatry
#17
JOURNAL ARTICLE
Rachel L Kember, Rachel Vickers-Smith, Hang Zhou, Heng Xu, Mariela Jennings, Cecilia Dao, Lea Davis, Sandra Sanchez-Roige, Amy C Justice, Joel Gelernter, Marijana Vujkovic, Henry R Kranzler
OBJECTIVE: Recent genome-wide association studies (GWASs) of alcohol-related phenotypes have uncovered key differences in the underlying genetic architectures of alcohol consumption and alcohol use disorder (AUD), with the two traits having opposite genetic correlations with psychiatric disorders. Understanding the genetic factors that underlie the transition from heavy drinking to AUD has important theoretical and clinical implications. METHODS: The authors used longitudinal data from the cross-ancestry Million Veteran Program sample to identify 1) novel loci associated with AUD and alcohol consumption (measured by the score on the consumption subscale of the Alcohol Use Disorders Identification Test [AUDIT-C]), 2) the impact of phenotypic variation on genetic discovery, and 3) genetic variants with direct effects on AUD that are not mediated through alcohol consumption...
August 1, 2023: American Journal of Psychiatry
#18
JOURNAL ARTICLE
Børge Holen, Alexey A Shadrin, Romain Icick, Tahir T Filiz, Guy Hindley, Linn Rødevand, Kevin S O'Connell, Espen Hagen, Oleksandr Frei, Shahram Bahrami, Weiqiu Cheng, Nadine Parker, Markos Tesfaye, Piotr Jahołkowski, Naz Karadag, Anders M Dale, Srdjan Djurovic, Olav B Smeland, Ole A Andreassen
Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, schizophrenia (SCZ), bipolar disorder (BD) and major depression (MD) of European ancestry...
June 2023: Addiction Biology
#19
JOURNAL ARTICLE
Heng Xu, Sylvanus Toikumo, Richard C Crist, Klaudia Glogowska, Zeal Jinwala, Joseph D Deak, Amy C Justice, Joel Gelernter, Emma C Johnson, Henry R Kranzler, Rachel L Kember
BACKGROUND AND AIMS: Genome-wide association studies (GWAS) of opioid use disorder (OUD) and cannabis use disorder (CUD) have lagged behind those of alcohol use disorder (AUD) and smoking, where many more loci have been identified. We sought to identify novel loci for substance use traits (SUTs) in both African- (AFR) and European- (EUR) ancestry individuals to enhance our understanding of the traits' genetic architecture. DESIGN: We used multi-trait analysis of GWAS (MTAG) to analyze four SUTs in EUR subjects (OUD, CUD, AUD and smoking initiation [SMKinitiation]), and three SUTs in AFR subjects (OUD, AUD and smoking trajectory [SMKtrajectory])...
May 8, 2023: Addiction
#20
JOURNAL ARTICLE
Henry R Kranzler, Richard Feinn, Heng Xu, Brendan L Ho, Divya Saini, Olivia R Nicastro, Anya Jacoby, Sylvanus Toikumo, Joel Gelernter, Emily E Hartwell, Rachel L Kember
BACKGROUND AND AIMS: Genetic risk can influence disease progression. We measured the impact of genetic risk for substance use disorders (SUDs) on substance use onset and progression of symptoms. DESIGN, SETTING, PARTICIPANTS: Using findings from genome-wide association studies (GWASs) of alcohol use disorder (AUD), opioid use disorder (OUD) and smoking trajectory (SMK) as discovery samples, we calculated polygenic risk scores (PRSs) in a deeply phenotyped independent target sample...
April 17, 2023: Addiction
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