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. 2008 Apr;13(4):417-28.
doi: 10.1038/sj.mp.4002147. Epub 2008 Jan 15.

Genotype patterns that contribute to increased risk for or protection from developing heroin addiction

D A Nielsen  1 , F Ji, V Yuferov, A Ho, A Chen, O Levran, J Ott, M J Kreek
Affiliations

Genotype patterns that contribute to increased risk for or protection from developing heroin addiction

D A Nielsen et al. Mol Psychiatry. 2008 Apr.

Abstract

A genome-wide association study was conducted using microarray technology to identify genes that may be associated with the vulnerability to develop heroin addiction, using DNA from 104 individual former severe heroin addicts (meeting Federal criteria for methadone maintenance) and 101 individual control subjects, all Caucasian. Using separate analyses for autosomal and X chromosomal variants, we found that the strongest associations of allele frequency with heroin addiction were with the autosomal variants rs965972, located in the Unigene cluster Hs.147755 (experiment-wise q=0.053), and rs1986513 (q=0.187). The three variants exhibiting the strongest association with heroin addiction by genotype frequency were rs1714984, located in an intron of the gene for the transcription factor myocardin (P=0.000022), rs965972 (P=0.000080) and rs1867898 (P=0.000284). One genotype pattern (AG-TT-GG) was found to be significantly associated with developing heroin addiction (odds ratio (OR)=6.25) and explained 27% of the population attributable risk for heroin addiction in this cohort. Another genotype pattern (GG-CT-GG) of these variants was found to be significantly associated with protection from developing heroin addiction (OR=0.13), and lacking this genotype pattern explained 83% of the population attributable risk for developing heroin addiction. Evidence was found for involvement of five genes in heroin addiction, the genes coding for the mu opioid receptor, the metabotropic receptors mGluR6 and mGluR8, nuclear receptor NR4A2 and cryptochrome 1 (photolyase-like). This approach has identified several new genes potentially associated with heroin addiction and has confirmed the role of OPRM1 in this disease.

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Figures

Figure 1
Figure 1
Distribution of the negative log10 P-values of the association of genotype and allele frequency with heroin addiction of each variant across the genome. The negative log10 P-values for the point-wise significance of the genotype frequency (pink squares) and allele frequency (blue diamonds) association analyses with heroin addiction (ordinate) are plotted versus their location on their respective chromosome in the genome in Mb (1 million bases) (abscissa). The two most significantly associated variants, with q-values of less than 0.2 by experiment-wise association of genotype or allele frequency with heroin addiction were rs965972 and rs1986513, which are located on chromosomes 1 and 4, respectively, and are indicated with ←.
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