Autosomal linkage analysis for cannabis use behaviors in Australian adults

Abstract

Cannabis is the most commonly used illicit drug in developed and in developing nations. Twin studies have highlighted the role of genetic influences on early stages of cannabis use, such as a lifetime history of use, early-onset use and frequent use, however, we are not aware of any genomic studies that have examined these phenotypes. Using data on 2314 families consisting of 5600 adult Australian offspring and their parents, all of whom were scanned using 1399 unique autosomal markers, we conducted autosomal linkage analyses for lifetime history of cannabis initiation, early-onset cannabis use and frequency of use, using a variance components approach in the linkage package MERLIN. Suggestive evidence for linkage was found on chromosome 18 (LOD 2.14 for frequency of use, LOD 1.97 for initiation, at 90-97 cM) and also on chromosome 19 (LOD 1.92 for early-onset at 17 cM). These LOD scores did not meet genome-wide significance. Further replication of these linkage regions in other samples will be required, although these initial results suggest further targeted efforts on chromosome 18 may yield interesting candidate genes for early stages of cannabis-related behaviors.

FIGURE 1

Linkage peaks (LOD score of y-axis and DeCode centiMorgan position on x-axis) for cannabis initiation (blue), early-onset (red) and frequency of use (green) for 22 autosomal markers. The x-axis for each chromosome is scaled for chromosomal length (i.e. x-axis is longest for chromosome 1 and shortest for chromosome 22), and triangles on the x-axis represent the position of the centromere. LOD=3.0 is denoted in each plot.