Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms

Abstract

Strong genetic contributions to drug abuse vulnerability are well documented, but few chromosomal locations for human drug-abuse vulnerability alleles have been confirmed. We now identify chromosomal markers whose alleles distinguish drug abusers from control individuals in each of two samples, on the basis of pooled-sample microarray and association analyses. Reproducibly positive chromosomal regions defined by these markers in conjunction with previous results were especially unlikely to have been identified by chance. Positive markers identify the alcohol dehydrogenase (ADH) locus, flank the brain-derived neurotropic factor (BDNF) locus, and mark seven other regions previously linked to vulnerability to nicotine or alcohol abuse. These data support polygenic contributions of common allelic variants to polysubstance abuse vulnerability.

Figure 1

Chromosome-by-chromosome distribution (labels 1–22 and X) of abuser/control ratios (y-axis) for SNPs positioned according to their average radiation-hybrid chromosomal distance in centimorgans (x-axis). Abuser/control ratios shown are from the European American sample. Red symbols indicate SNPs with results in the upper or lower 5% of the distribution of values. Labeled symbols indicate SNPs with outlying abuser/control values in both European American and African American samples. Green symbols indicate the positions of reproducibly positive SNPs with adjacent chromosomal positions, on the basis of NCBI Mapviewer coordinates.