Genome-wide association study of a quantitative disordered gambling trait.
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.
Quantitative Genetics, Queensland Institute of Medical Research, Brisbane, QLD, Australia.
Penelope A
PA
Lind
Gu
G
Zhu
Grant W
GW
Montgomery
Pamela A F
PA
Madden
Andrew C
AC
Heath
Nicholas G
NG
Martin
Wendy S
WS
Slutske
D000328:Adult; D000067696:Ataxin-1; D000067528:Ataxins; D016022:Case-Control Studies; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D018491:Dopamine Agonists / Q000009:adverse effects; D005260:Female; D005715:Gambling / Q000235:genetics*; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000523:psychology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011973:Receptors, LDL / Q000235:genetics*
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D018491:Dopamine Agonists; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011973:Receptors, LDL; C036053:VLDL receptor; C581554:metallothionein1X, human; D008668:Metallothionein