Genome-wide linkage analysis of heroin dependence in Han Chinese: results from wave one of a multi-stage study

Abstract

The contribution of genes to the etiology of heroin dependence is greater than for any other illicit drug. The specific genes mediating this effect remain unknown, despite several candidate gene association studies of the condition. Here we report the results of a genome-wide search for heroin dependence susceptibility loci using multipoint linkage analysis. In phase I, we ascertained 207 independent affected sibling pairs from 202 Han Chinese families from Yunnan Province, China (near Asia's "Golden Triangle"). After data-cleaning, 194 fully independent sibling pairs (i.e., with no overlapping individuals) from 192 families were genotyped on 404 short tandem-repeat markers spaced at an average inter-marker distance of 9 cM. Although none of our findings achieved genome-wide significance, we found two regions with non-parametric linkage (NPL) Z-scores greater than 2.0. An NPL Z-score of 2.19 (uncorrected P-value = 0.014) was observed at D4S1644, located at 143.3 cM on chromosomal region 4q31.21. The highest NPL Z-score of 2.36 (uncorrected P-value = 0.009) was observed at 53.4 cM on chromosomal region 17q11.2 at marker D17S1880. This is among the first published reports of a genome-wide linkage analysis of heroin dependence. Forthcoming results from other groups and from two additional waves of ascertainment (one planned, one currently ongoing) for our own study should be able to support or refute the putative susceptibility loci we have identified, after which positional candidate genes can be further evaluated as risk factors for the illness.

Figure 1

The plot shows a curve of NPL Z-scores observed at markers mapping to the indicated centiMorgan positions throughout the genome.

Figure 2

The plot shows a curve of NPL Z-scores observed at markers mapping to the indicated centiMorgan positions on chromosome 4, including a peak NPL Z-score of 2.19 at marker D4S1644 (143.3 cM).

Figure 3

The plot shows a curve of NPL Z-scores observed at markers mapping to the indicated centiMorgan positions on chromosome 17, including a peak NPL Z-score of 2.36 at marker D17S1880 (53.4 cM).