Whole genome sequence study of cannabis dependence in two independent cohorts

Ian R. Gizer, Chris Bizon, David A. Gilder, Cindy L. Ehlers, Kirk C. Wilhelmsen

Research output: Contribution to journalArticle

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Abstract

Recent advances in genome wide sequencing techniques and analytical methods allow for more comprehensive examinations of the genome than microarray-based genome-wide association studies (GWAS). The present report provides the first application of whole genome sequencing (WGS) to identify low frequency variants involved in cannabis dependence across two independent cohorts. The present study used low-coverage whole genome sequence data to conduct set-based association and enrichment analyses of low frequency variation in protein-coding regions as well as regulatory regions in relation to cannabis dependence. Two cohorts were studied: a population-based Native American tribal community consisting of 697 participants nested within large multi-generational pedigrees and a family-based sample of 1832 predominantly European ancestry participants largely nested within nuclear families. Participants in both samples were assessed for Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) lifetime cannabis dependence, with 168 and 241 participants receiving a positive diagnosis in each sample, respectively. Sequence kernel association tests identified one protein-coding region, C1orf110 and one regulatory region in the MEF2B gene that achieved significance in a meta-analysis of both samples. A regulatory region within the PCCB gene, a gene previously associated with schizophrenia, exhibited a suggestive association. Finally, a significant enrichment of regions within or near genes with multiple splice variants or involved in cell adhesion or potassium channel activity were associated with cannabis dependence. This initial study demonstrates the potential utility of low pass whole genome sequencing for identifying genetic variants involved in the etiology of cannabis use disorders.

LanguageEnglish (US)
Pages461-473
Number of pages13
JournalAddiction Biology
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Marijuana Abuse
Genome
Nucleic Acid Regulatory Sequences
Open Reading Frames
Genes
North American Indians
Genome-Wide Association Study
Potassium Channels
Cannabis
Pedigree
Nuclear Family
Cell Adhesion
Diagnostic and Statistical Manual of Mental Disorders
Meta-Analysis
Schizophrenia
Population

Keywords

  • cannabis
  • genetic association
  • genetics
  • marijuana dependence
  • whole genome sequencing

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Whole genome sequence study of cannabis dependence in two independent cohorts. / Gizer, Ian R.; Bizon, Chris; Gilder, David A.; Ehlers, Cindy L.; Wilhelmsen, Kirk C.

In: Addiction Biology, Vol. 23, No. 1, 01.01.2018, p. 461-473.

Research output: Contribution to journalArticle

Gizer, IR, Bizon, C, Gilder, DA, Ehlers, CL & Wilhelmsen, KC 2018, 'Whole genome sequence study of cannabis dependence in two independent cohorts' Addiction Biology, vol. 23, no. 1, pp. 461-473. DOI: 10.1111/adb.12489
Gizer IR, Bizon C, Gilder DA, Ehlers CL, Wilhelmsen KC. Whole genome sequence study of cannabis dependence in two independent cohorts. Addiction Biology. 2018 Jan 1;23(1):461-473. Available from, DOI: 10.1111/adb.12489
Gizer, Ian R. ; Bizon, Chris ; Gilder, David A. ; Ehlers, Cindy L. ; Wilhelmsen, Kirk C./ Whole genome sequence study of cannabis dependence in two independent cohorts. In: Addiction Biology. 2018 ; Vol. 23, No. 1. pp. 461-473
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