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. 2013 May;18(3):511-22.
doi: 10.1111/j.1369-1600.2012.00463.x. Epub 2012 Jul 11.

Genome-wide Association Study of a Quantitative Disordered Gambling Trait

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Free PMC article

Genome-wide Association Study of a Quantitative Disordered Gambling Trait

Penelope A Lind et al. Addict Biol. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Manhatten plot for the quantitative disordered gambling factor score (DG). The vertical axis shows the −log10 of the association P-values and the horizontal axis shows the whole autosomal genome divided into 22 autosomes and the X chromosome.
Figure 2
Figure 2
Quantile-Quantile (Q-Q) plot for the quantitative disordered gambling factor score (genomic inflation λ = 0.997). The horizontal axis shows the −log10 of expected P-values of association from a 1 d.f. chi-square distribution and the vertical axis shows the −log10 of P-values from the observed chi-square distribution. The shaded region represents the 95% confidence interval of the expected chi-square statistics under the null hypothesis of no association.

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