scholarly journals Genome-wide association study implicates CHRNA2 in cannabis use disorder

2017 ◽  
Author(s):  
Ditte Demontis ◽  
Veera Manikandan Rajagopal ◽  
Thomas D. Als ◽  
Jakob Grove ◽  
Jonatan Pallesen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Significant Risk ◽  
The United States ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide ◽  
Independent Population ◽  
A Genome

Introductory paragraphCannabis is the most frequently used illicit psychoactive substance worldwide1. Life time use has been reported among 35-40% of adults in Denmark2 and the United States3. Cannabis use is increasing in the population4–6 and among users around 9% become dependent7. The genetic risk component is high with heritability estimates of 518–70%9. Here we report the first genome-wide significant risk locus for cannabis use disorder (CUD, P=9.31×10−12) that replicates in an independent population (Preplication=3.27×10−3, Pmetaanalysis=9.09×10−12). The finding is based on a genome-wide association study (GWAS) of 2,387 cases and 48,985 controls followed by replication in 5,501 cases and 301,041 controls. The index SNP (rs56372821) is a strong eQTL for CHRNA2 and analyses of the genetic regulated gene expressions identified significant association of CHRNA2 expression in cerebellum with CUD. This indicates a potential therapeutic use in CUD of compounds with agonistic effect on the neuronal acetylcholine receptor alpha-2 subunit encoded by CHRNA2. At the polygenic level analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.

scholarly journals Genome-wide association study implicates CHRNA2 in cannabis use disorder

2019 ◽  
Vol 22 (7) ◽  
pp. 1066-1074 ◽  
Author(s):  
Ditte Demontis ◽  
Veera Manikandan Rajagopal ◽  
Thorgeir E. Thorgeirsson ◽  
Thomas D. Als ◽  
Jakob Grove ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide

GENOME-WIDE ASSOCIATION STUDY OF CANNABIS USE DISORDER IN EUROPEAN AND AFRICAN ANCESTRIES

2019 ◽  
Vol 29 ◽  
pp. S10-S11
Author(s):  
Emma Johnson ◽  
Ditte Demontis ◽  
Renato Polimanti ◽  
Raymond Walters ◽  
Jeanette McClintick ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide

Cannabis use and schizophrenia: Chicken or egg?

2018 ◽  
Vol 10 (460) ◽  
pp. eaav0342
Author(s):  
Laura C. Andreae
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Risk Genes ◽  
Genome Wide ◽  
A Genome

A genome-wide association study identifies risk genes for cannabis use and examines direction of causality for its association with schizophrenia.

scholarly journals A large-scale genome-wide association study meta-analysis of cannabis use disorder

2020 ◽  
Vol 7 (12) ◽  
pp. 1032-1045 ◽  
Author(s):  
Emma C Johnson ◽  
Ditte Demontis ◽  
Thorgeir E Thorgeirsson ◽  
Raymond K Walters ◽  
Renato Polimanti ◽  
...  
Keyword(s):  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide

scholarly journals GENOME-WIDE ASSOCIATION STUDY IMPLICATES CHRNA2 IN CANNABIS USE DISORDER

2019 ◽  
Vol 29 ◽  
pp. S1023 ◽  
Author(s):  
Ditte Demontis ◽  
Veera Rajagopal ◽  
Thorgeir Thorgeirsson ◽  
Thomas Als ◽  
Jakob Grove ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Cannabis Use ◽  
Genome Wide Association ◽  
Cannabis Use Disorder ◽  
Genome Wide

scholarly journals Genome-wide association study reveals an independent genetic basis of zinc and cadmium concentrations in fresh sweet corn kernels

2021 ◽  
Author(s):  
Matheus Baseggio ◽  
Matthew Murray ◽  
Di Wu ◽  
Gregory Ziegler ◽  
Nicholas Kaczmar ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Sweet Corn ◽  
The United States ◽  
Zinc Homeostasis ◽  
Genome Wide Association ◽  
Elemental Profile ◽  
Genome Wide ◽  
A Genome ◽  
Corn Kernels

AbstractDespite being one of the most consumed vegetables in the United States, the elemental profile of sweet corn (Zea mays L.) is limited in its dietary contributions. To address this through genetic improvement, a genome-wide association study was conducted for the concentrations of 15 elements in fresh kernels of a sweet corn association panel. In concordance with mapping results from mature maize kernels, we detected a probable pleiotropic association of zinc and iron concentrations with nicotianamine synthase5 (nas5), which purportedly encodes an enzyme involved in synthesis of the metal chelator nicotianamine. Additionally, a pervasive association signal was identified for cadmium concentration within a recombination suppressed region on chromosome 2. The likely causal gene underlying this signal was heavy metal ATPase 3 (hma3), whose counterpart in rice, OsHMA3, mediates vacuolar sequestration of cadmium and zinc in roots, whereby regulating zinc homeostasis and cadmium accumulation in grains. Consistent with transgenic studies in rice, we detected an association of hma3 with cadmium but not zinc accumulation in fresh kernels. This finding implies that selection for low cadmium will not affect zinc levels in fresh kernels. Although less resolved association signals were detected for boron, nickel, and calcium, all 15 elements were shown to have moderate predictive abilities via whole- genome prediction. Collectively, these results help improve our genomics-assisted breeding efforts centered on improving the elemental profile of fresh sweet corn kernels.

scholarly journals Genome-Wide Association Study of Opioid Cessation

2020 ◽  
Vol 9 (1) ◽  
pp. 180 ◽  
Author(s):  
Jiayi W. Cox ◽  
Richard M. Sherva ◽  
Kathryn L. Lunetta ◽  
Emma C. Johnson ◽  
Nicholas G. Martin ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Chronic Back Pain ◽  
The United States ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Scores ◽  
Opioid Use ◽  
Genome Wide ◽  
A Genome

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (pAA + EA = 2.24 × 10−6), rs36098404 in MYOM2 (pEA = 2.24 × 10−6), and rs592026 in SNAP25-AS1 (pEA = 6.53 × 10−6). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10−2) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10−2). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD.

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