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JOURNAL ARTICLE
Qian Peng, Kirk C Wilhelmsen, Cindy L Ehlers
Cannabis use disorder (CUD) is common and has in part a genetic basis. The risk factors underlying its development likely involve multiple genes that are polygenetic and interact with each other and the environment to ultimately lead to the disorder. Co-morbidity and genetic correlations have been identified between CUD and other disorders and traits in select populations primarily of European descent. If two or more traits, such as CUD and another disorder, are affected by the same genetic locus, they are said to be pleiotropic...
April 14, 2023: Molecular and Cellular Neurosciences
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JOURNAL ARTICLE
Fang Chen, Xingyan Wang, Seon-Kyeong Jang, Bryan C Quach, J Dylan Weissenkampen, Chachrit Khunsriraksakul, Lina Yang, Renan Sauteraud, Christine M Albert, Nicholette D D Allred, Donna K Arnett, Allison E Ashley-Koch, Kathleen C Barnes, R Graham Barr, Diane M Becker, Lawrence F Bielak, Joshua C Bis, John Blangero, Meher Preethi Boorgula, Daniel I Chasman, Sameer Chavan, Yii-Der I Chen, Lee-Ming Chuang, Adolfo Correa, Joanne E Curran, Sean P David, Lisa de Las Fuentes, Ranjan Deka, Ravindranath Duggirala, Jessica D Faul, Melanie E Garrett, Sina A Gharib, Xiuqing Guo, Michael E Hall, Nicola L Hawley, Jiang He, Brian D Hobbs, John E Hokanson, Chao A Hsiung, Shih-Jen Hwang, Thomas M Hyde, Marguerite R Irvin, Andrew E Jaffe, Eric O Johnson, Robert Kaplan, Sharon L R Kardia, Joel D Kaufman, Tanika N Kelly, Joel E Kleinman, Charles Kooperberg, I-Te Lee, Daniel Levy, Sharon M Lutz, Ani W Manichaikul, Lisa W Martin, Olivia Marx, Stephen T McGarvey, Ryan L Minster, Matthew Moll, Karine A Moussa, Take Naseri, Kari E North, Elizabeth C Oelsner, Juan M Peralta, Patricia A Peyser, Bruce M Psaty, Nicholas Rafaels, Laura M Raffield, Muagututi'a Sefuiva Reupena, Stephen S Rich, Jerome I Rotter, David A Schwartz, Aladdin H Shadyab, Wayne H-H Sheu, Mario Sims, Jennifer A Smith, Xiao Sun, Kent D Taylor, Marilyn J Telen, Harold Watson, Daniel E Weeks, David R Weir, Lisa R Yanek, Kendra A Young, Kristin L Young, Wei Zhao, Dana B Hancock, Bibo Jiang, Scott Vrieze, Dajiang J Liu
Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods...
January 26, 2023: Nature Genetics
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JOURNAL ARTICLE
Kenneth Blum, David Han, Abdalla Bowirrat, Bernard William Downs, Debasis Bagchi, Panayotis K Thanos, David Baron, Eric R Braverman, Catherine A Dennen, Ashim Gupta, Igor Elman, Rajendra D Badgaiyan, Luis Llanos-Gomez, Jag Khalsa, Debmalya Barh, Thomas McLaughlin, Mark S Gold
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum's group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles...
October 27, 2022: Journal of Personalized Medicine
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JOURNAL ARTICLE
Arvin Haghighatfard, Amir Hossein Ghaderi, Parmida Mostajabi, Seyedeh Sara Kashfi, Hediyeh Mohabati Somehsarayee, Maryam Shahrani, Mahla Mehrasa, Saba Haghighat, Mahdi Farhadi, Maryam Momayez Sefat, Atena Alsadat Shiryazdi, Naghmeh Ezzati, Masoume Ghasemzadeh Qazvini, Atie Alizadenik, Elham Rastegari Moghadam
BACKGROUND: Internet addiction disorder (IAD) is listed as a disorder requiring further studies in the diagnostic and statistical manual of mental disorders (DSM-V). Psychological studies showed significant co-morbidity of IAD with depression, alcohol abuse, and anxiety disorder. Etiology and genetic bases of IAD are unclear. AIMS: Present study aimed to investigate the genetic, psychological, and cognitive bases of a tendency to internet addiction. METHODS AND PROCEDURES: DNA was extracted from blood samples of IADs (N = 16,520) and 18,000 matched non-psychiatric subjects...
December 23, 2022: Research in Developmental Disabilities
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JOURNAL ARTICLE
Anastasia Levchenko, Sergey Malov, Alexey Antonik, Anastasia Protsvetkina, Kseniya V Rybakova, Alexander Kanapin, Alexey N Yakovlev, Anna Y Nenasteva, Anton E Nikolishin, Nikolay Cherkasov, Natalia A Chuprova, Anna S Blagonravova, Angelica V Sergeeva, Tatyana V Zhilyaeva, Maria K Denisenko, Raul R Gainetdinov, Alexander O Kibitov, Evgeny M Krupitsky
At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD ( p -value = 1.33 × 10-8 calculated with the Yates-corrected χ2 test under the assumption of dominant inheritance) was discovered in female patients...
November 22, 2022: Biomedicines
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JOURNAL ARTICLE
Nathan A Kimbrel, Allison E Ashley-Koch, Xue J Qin, Jennifer H Lindquist, Melanie E Garrett, Michelle F Dennis, Lauren P Hair, Jennifer E Huffman, Daniel A Jacobson, Ravi K Madduri, Jodie A Trafton, Hilary Coon, Anna R Docherty, Niamh Mullins, Douglas M Ruderfer, Philip D Harvey, Benjamin H McMahon, David W Oslin, Jean C Beckham, Elizabeth R Hauser, Michael A Hauser
IMPORTANCE: Suicide is a leading cause of death; however, the molecular genetic basis of suicidal thoughts and behaviors (SITB) remains unknown. OBJECTIVE: To identify novel, replicable genomic risk loci for SITB. DESIGN, SETTING, AND PARTICIPANTS: This genome-wide association study included 633 778 US military veterans with and without SITB, as identified through electronic health records. GWAS was performed separately by ancestry, controlling for sex, age, and genetic substructure...
February 1, 2023: JAMA Psychiatry
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JOURNAL ARTICLE
Darius M Bost, Chris Bizon, Jeffrey L Tilson, Dayne L Filer, Ian R Gizer, Kirk C Wilhelmsen
INTRODUCTION: Genome-wide association studies (GWAS) have played a critical role in identifying many thousands of loci associated with complex phenotypes and diseases. This has led to several translations of novel disease susceptibility genes into drug targets and care. This however has not been the case for analyses where sample sizes are small, which suffer from multiple comparisons testing. The present study examined the statistical impact of combining a burden test methodology, PrediXcan, with a multimodel meta-analysis, cross phenotype association (CPASSOC)...
September 2022: Complex psychiatry
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JOURNAL ARTICLE
Bolun Cheng, Chuyu Pan, Shiqiang Cheng, Peilin Meng, Li Liu, Wenming Wei, Xuena Yang, Yumeng Jia, Yan Wen, Feng Zhang
Habitual coffee consumption is an addictive behavior with unknown genetic variations and has raised public health issues about its potential health-related outcomes. We performed exome-wide association studies to identify rare risk variants contributing to habitual coffee consumption utilizing the newly released UK Biobank exome dataset ( n = 200,643). A total of 34,761 qualifying variants were imported into SKAT to conduct gene-based burden and robust tests with minor allele frequency <0.01, adjusting the polygenic risk scores (PRS) of coffee intake to exclude the effect of common coffee-related polygenic risk...
October 16, 2022: Nutrients
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JOURNAL ARTICLE
Nathan Gaddis, Ravi Mathur, Jesse Marks, Linran Zhou, Bryan Quach, Alex Waldrop, Orna Levran, Arpana Agrawal, Matthew Randesi, Miriam Adelson, Paul W Jeffries, Nicholas G Martin, Louisa Degenhardt, Grant W Montgomery, Leah Wetherill, Dongbing Lai, Kathleen Bucholz, Tatiana Foroud, Bernice Porjesz, Valgerdur Runarsdottir, Thorarinn Tyrfingsson, Gudmundur Einarsson, Daniel F Gudbjartsson, Bradley Todd Webb, Richard C Crist, Henry R Kranzler, Richard Sherva, Hang Zhou, Gary Hulse, Dieter Wildenauer, Erin Kelty, John Attia, Elizabeth G Holliday, Mark McEvoy, Rodney J Scott, Sibylle G Schwab, Brion S Maher, Richard Gruza, Mary Jeanne Kreek, Elliot C Nelson, Thorgeir Thorgeirsson, Kari Stefansson, Wade H Berrettini, Joel Gelernter, Howard J Edenberg, Laura Bierut, Dana B Hancock, Eric Otto Johnson
Opioid addiction (OA) is moderately heritable, yet only rs1799971, the A118G variant in OPRM1, has been identified as a genome-wide significant association with OA and independently replicated. We applied genomic structural equation modeling to conduct a GWAS of the new Genetics of Opioid Addiction Consortium (GENOA) data together with published studies (Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health), comprising 23,367 cases and effective sample size of 88,114 individuals of European ancestry...
October 7, 2022: Scientific Reports
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JOURNAL ARTICLE
Kenneth Blum, David Han, Ashim Gupta, David Baron, Eric R Braverman, Catherine A Dennen, Shan Kazmi, Luis Llanos-Gomez, Rajendra D Badgaiyan, Igor Elman, Panayotis K Thanos, Bill W Downs, Debasis Bagchi, Marjorie C Gondre-Lewis, Mark S Gold, Abdalla Bowirrat
Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in JAMA , there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), Blum's group developed the Genetic Addiction Risk Severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions published from 1990 until 2021...
August 26, 2022: Journal of Personalized Medicine
#31
JOURNAL ARTICLE
Xiaoqiang Shi, Wenji Yuan, Qingyi Cao, Wenyan Cui
BACKGROUND AND AIMS: Disproportionately high rates of smoking have been found in low-income communities, but the causal direction and role of education in this relationship remains less well understood. Here, we used bidirectional Mendelian randomization (MR) to measure the causal relationships between smoking, income and education. DESIGN: Two-sample univariable and multivariable MR analyses were conducted to evaluate the total and direct effect of income and education on tobacco smoking...
August 5, 2022: Addiction
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REVIEW
Evangelia Eirini Tsermpini, Anja Plemenitaš Ilješ, Vita Dolžan
Alcohol use disorder (AUD) is a highly prevalent, comorbid, and disabling disorder. The underlying mechanism of ethanol neurotoxicity and the involvement of oxidative stress is still not fully elucidated. However, ethanol metabolism has been associated with increased oxidative stress through alcohol dehydrogenase, the microsomal ethanol oxidation system, and catalase metabolic pathways. We searched the PubMed and genome-wide association studies (GWAS) catalog databases to review the literature systematically and summarized the findings focusing on AUD and alcohol abstinence in relation to oxidative stress...
July 15, 2022: Antioxidants (Basel, Switzerland)
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JOURNAL ARTICLE
Joseph D Deak, Hang Zhou, Marco Galimberti, Daniel F Levey, Frank R Wendt, Sandra Sanchez-Roige, Alexander S Hatoum, Emma C Johnson, Yaira Z Nunez, Ditte Demontis, Anders D Børglum, Veera M Rajagopal, Mariela V Jennings, Rachel L Kember, Amy C Justice, Howard J Edenberg, Arpana Agrawal, Renato Polimanti, Henry R Kranzler, Joel Gelernter
Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) of OUD to date have yielded few susceptibility loci. We performed a large-scale GWAS of OUD in individuals of European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis of GWAS) with genetically correlated substance use disorders (SUDs). Meta-analysis included seven cohorts: the Million Veteran Program, Psychiatric Genomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU, and Yale-Penn 3, resulting in a total N = 639,063 (Ncases = 20,686;Neffective = 77,026) across ancestries...
July 25, 2022: Molecular Psychiatry
#34
JOURNAL ARTICLE
Jiahui Hou, Jonathan L Hess, Nicola Armstrong, Joshua C Bis, Benjamin Grenier-Boley, Ida K Karlsson, Ganna Leonenko, Katya Numbers, Eleanor K O'Brien, Alexey Shadrin, Anbupalam Thalamuthu, Qiong Yang, Ole A Andreassen, Henry Brodaty, Margaret Gatz, Nicole A Kochan, Jean-Charles Lambert, Simon M Laws, Colin L Masters, Karen A Mather, Nancy L Pedersen, Danielle Posthuma, Perminder S Sachdev, Julie Williams, Chun Chieh Fan, Stephen V Faraone, Christine Fennema-Notestine, Shu-Ju Lin, Valentina Escott-Price, Peter Holmans, Sudha Seshadri, Ming T Tsuang, William S Kremen, Stephen J Glatt
Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast "resilient" unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk...
July 25, 2022: Translational Psychiatry
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JOURNAL ARTICLE
Spencer B Huggett, Ami S Ikeda, John E McGeary, Karla R Kaun, Rohan H C Palmer
Opiate/opioid use disorder (OUD) is a chronic relapsing brain disorder that has increased in prevalence in the last two decades in the United States. Understanding the molecular correlates of OUD may provide key insights into the pathophysiology of this syndrome. Using publicly available RNA-sequencing data, our study investigated the possible role of alternative mRNA splicing in human brain tissue (dorsal-lateral prefrontal cortex (dlPFC), nucleus accumbens (NAc), and midbrain) of 90 individuals with OUD or matched controls...
June 10, 2022: Genes
#36
REVIEW
Alasdair MacKenzie, Elizabeth A Hay, Andrew R McEwan
Alcohol use disorder (AUD) is one of the major causes of mortality and morbidity world-wide. It is estimated that 50% of the causes of AUD are heritable. Efforts to determine the genetic determinants governing AUD using genome wide association studies (GWAS) show that the most strongly associated SNPs occur within, or in the vicinity of, genes encoding enzymes that metabolise ethanol. However, these studies were not so conclusive in identifying the genes that influenced the choice to drink ethanol or why a proportion of the population become addicted...
June 2022: Addict Neurosci
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JOURNAL ARTICLE
F K El Banna, J M Otto, S M Mulloy, W Tsai, S M McElroy, A L Wong, G Cutts, S I Vrieze, A M Lee
Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder...
June 4, 2022: Scientific Reports
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JOURNAL ARTICLE
Jacob A Beierle, Emily J Yao, Stan I Goldstein, Julia L Scotellaro, Katherine D Sena, Olga Averin, David E Moody, Christopher A Reilly, Andrew Emili, Gary Peltz, Martin T Ferris, Camron D Bryant
Understanding the pharmacokinetic profile of an opioid drug is vital to therapeutic success, and mutations in human PK genes can drastically alter therapeutic efficacy of opioids. We observed that at 30 min post-oxycodone administration (1.25 mg/kg, i.p.) BALB/cJ mice showed a higher whole brain concentration of oxycodone, and female specific increase in noroxycodone, and oxymorphone compared to BALB/cByJ. This observation could explain the sex-specific increase in oxycodone state-dependent conditioned place preference in BALB/cJ female mice...
May 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
#39
JOURNAL ARTICLE
Lea Zillich, Eric Poisel, Josef Frank, Jerome C Foo, Marion M Friske, Fabian Streit, Lea Sirignano, Stefanie Heilmann-Heimbach, André Heimbach, Per Hoffmann, Franziska Degenhardt, Anita C Hansson, Georgy Bakalkin, Markus M Nöthen, Marcella Rietschel, Rainer Spanagel, Stephanie H Witt
Alcohol Use Disorder (AUD) is a major contributor to global mortality and morbidity. Postmortem human brain tissue enables the investigation of molecular mechanisms of AUD in the neurocircuitry of addiction. We aimed to identify differentially expressed (DE) genes in the ventral and dorsal striatum between individuals with AUD and controls, and to integrate the results with findings from genome- and epigenome-wide association studies (GWAS/EWAS) to identify functionally relevant molecular mechanisms of AUD...
May 6, 2022: Translational Psychiatry
#40
JOURNAL ARTICLE
Xiang-Wen Chang, Yan Sun, Jia-Na Muhai, Yang-Yang Li, Yun Chen, Lin Lu, Su-Hua Chang, Jie Shi
BACKGROUND AND AIMS: Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome-wide findings is lacking for substance use. Here, we combined all the genome-wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs. METHODS: Systemic literature search for genome-wide association (GWAS) and RNA-seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog...
September 2022: Addiction
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