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Recent Advances in Cannabinoid Physiology and Pathology pp 129–150Cite as

Genetic Factors in Cannabinoid Use and Dependence

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1162))

Abstract

Cannabinoid use and dependence are heritable traits controlled in part by genetic factors. Despite a high incidence of use worldwide, genes that contribute to the risk of problematic use and dependence remain enigmatic. Here we review human candidate gene association studies, family-based linkage studies, and genome-wide association studies completed within the last two decades. These studies have expanded the list of candidate genes and intervals. However, there is little overlap between studies and generally low reproducibility in independent samples. Reasons for this lack of coherence vary but may depend on low sample size and statistical power, and the fact that most studies leverage populations ascertained for drug dependence other than cannabis. However, recent well-powered studies on lifetime cannabis use demonstrate that the genetic architecture of cannabis use resembles that of other substance use disorders and psychiatric disease in that many small effect genes contribute in an additive fashion. This finding suggests that increasing sample size and more focused recruitment of individuals based on cannabinoid use and dependence will identify more candidate genes. Follow-up of existing high priority candidates in preclinical model systems will facilitate better understanding of the genetic architecture and genetic risk factors for cannabis use and dependence.

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Abbreviations

2-AG:

2-arachidonoylglycerol

AA:

African American

AEA:

N-arachidonylethanolamide or anandamide

CADM2 :

cell adhesion molecule 2

CB1:

cannabinoid receptor type 1

CB2:

cannabinoid receptor type 2

CD:

cannabis dependence

CGAS:

candidate gene association studies

Chr:

chromosome

CNR1 :

gene encoding CB1

CUD:

cannabinoid use disorder

DAG:

1,2-diacylglycerol

DSM:

Diagnostic and Statistical Manual of Mental Disorders

EA:

European Americans

FAAH:

fatty acid amide hydrolase

FLS:

family-based linkage studies

GPCR:

G-protein coupled receptor

GTEx:

Genotype-Tissue Expression

GWAS:

genome-wide association studies

iPSYCH:

Initiative for Integrative Psychiatric Research

LD:

linkage disequilibrium

LOD:

logarithm of the odds

MGLL:

monoacylglycerol lipase

nAChR:

neuronal acetylcholine receptor

NAG:

Nicotine Addiction Genetics Program

NAPE-PLD:

N-acylphosphatidylethanolamine-specific phospholipase D

NCAM1 :

neural cell adhesion molecule 1

NRG1 :

neuregulin 1

PPAR:

peroxisome proliferator-act ivated receptor

SCOC:

short coiled-coil protein

SCOC-AS1 :

short coiled-coil protein anti-sense RNA 1

SNP:

single nucleotide polymorphism

THC:

Δ9-tetrahydrocannabinol

TRP:

transient receptor potential (ion channel)

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Authors and Affiliations

  1. Department of Genetics, Genomics and Informatics, The University of Tennessee Health Science Center, Memphis, TN, USA

    Megan K. Mulligan

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Correspondence to Megan K. Mulligan .

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  1. Department of Pharmacology, College of Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA

    Anna N. Bukiya

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Mulligan, M.K. (2019). Genetic Factors in Cannabinoid Use and Dependence. In: Bukiya, A. (eds) Recent Advances in Cannabinoid Physiology and Pathology. Advances in Experimental Medicine and Biology, vol 1162. Springer, Cham. https://doi.org/10.1007/978-3-030-21737-2_7

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