Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
22780124
TITLE
Genome-wide association study of a quantitative disordered gambling trait.
ABSTRACT
Disordered gambling is a moderately heritable trait, but the underlying genetic basis is largely unknown. We performed a genome-wide association study (GWAS) for disordered gambling using a quantitative factor score in 1312 twins from 894 Australian families. Association was conducted for 2 381 914 single-nucleotide polymorphisms (SNPs) using the family-based association test in Merlin followed by gene and pathway enrichment analyses. Although no SNP reached genome-wide significance, six achieved P-values < 1 × 10(-5) with variants in three genes (MT1X, ATXN1 and VLDLR) implicated in disordered gambling. Secondary case-control analyses found two SNPs on chromosome 9 (rs1106076 and rs12305135 near VLDLR) and rs10812227 near FZD10 on chromosome 12 to be significantly associated with lifetime Diagnostic and Statistical Manual of Mental Disorders, fourth edition pathological gambling and South Oaks Gambling Screen classified probable pathological gambling status. Furthermore, several addiction-related pathways were enriched for SNPs associated with disordered gambling. Finally, gene-based analysis of 24 candidate genes for dopamine agonist-induced gambling in individuals with Parkinson's disease suggested an enrichment of SNPs associated with disordered gambling. We report the first GWAS of disordered gambling. While further replication is required, the identification of susceptibility loci and biological pathways will be important in characterizing the biological mechanisms that underpin disordered gambling.
© 2012 The Authors. Addiction Biology © 2012 Society for the Study of Addiction.
DATE PUBLISHED
2013 May
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2012/07/11
entrez 2012/07/12 06:00
pubmed 2012/07/12 06:00
medline 2013/10/18 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lind PA Lind Penelope A PA Quantitative Genetics, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Zhu G Zhu Gu G
Montgomery GW Montgomery Grant W GW
Madden PA Madden Pamela A F PA
Heath AC Heath Andrew C AC
Martin NG Martin Nicholas G NG
Slutske WS Slutske Wendy S WS
INVESTIGATORS
JOURNAL
VOLUME: 18
ISSUE: 3
TITLE: Addiction biology
ISOABBREVIATION: Addict Biol
YEAR: 2013
MONTH: May
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1369-1600
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addict Biol
COUNTRY: United States
ISSNLINKING: 1355-6215
NLMUNIQUEID: 9604935
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Twin Study
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA011998 NIAAA NIH HHS United States
AA013320 NIAAA NIH HHS United States
AA013321 NIAAA NIH HHS United States
AA013326 NIAAA NIH HHS United States
AA014041 NIAAA NIH HHS United States
AA017688 NIAAA NIH HHS United States
DA012854 NIDA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
P50 AA011998 NIAAA NIH HHS United States
P60 AA011998 NIAAA NIH HHS United States
R01 AA013320 NIAAA NIH HHS United States
R01 AA013321 NIAAA NIH HHS United States
R01 AA013326 NIAAA NIH HHS United States
R01 AA014041 NIAAA NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 MH066206 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Ataxin-1
Ataxins
Case-Control Studies
Chromosomes, Human, Pair 12 genetics
Chromosomes, Human, Pair 9 genetics
Dopamine Agonists adverse effects
Female adverse effects
Gambling genetics
Genetic Markers genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Metallothionein genetics
Nerve Tissue Proteins genetics
Nuclear Proteins genetics
Parkinson Disease psychology
Polymorphism, Single Nucleotide genetics
Receptors, LDL genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 ATXN1 protein, human
0 Ataxin-1
0 Ataxins
0 Dopamine Agonists
0 Genetic Markers
0 Nerve Tissue Proteins
0 Nuclear Proteins
0 Receptors, LDL
0 VLDL receptor
0 metallothionein1X , human
9038-94-2 Metallothionein
OTHER ID's
OTHERID SOURCE
NIHMS369965 NLM
PMC3470766 NLM
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Last Modified: Oct 15 2007