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Updated: May 18, 2026

Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
Genetic analysis of AUTS2 as a susceptibility gene of heroin dependence
Yun-Hsiang Chen1, Ding-Lieh Liao, Chih-Hao Lai
1Division of Mental Health and Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
Background:
Both alcoholism and heroin dependence are common substance use disorders with a high genetic basis. A recent genetic study reported that the autism susceptibility candidate 2 gene (AUTS2) was involved in regulating the alcohol drinking behavior. In our previous total gene expression profiling study, we found that the AUTS2 transcript was significantly down-regulated in lymphoblastoid cell lines (LCL) in heroin dependent individuals compared with control subjects, which prompted us to investigate whether AUTS2 is associated with heroin dependence.
Methods:
We compared the AUTS2 transcript level of LCL between 124 heroin dependent males and 116 control males using real-time quantitative PCR, and conducted a genetic association study of the rs6943555 of AUTS2 with heroin dependence using a sample of 546 heroin dependent males and 373 control males.
Results:
We first verified that the average transcript level of AUTS2 in the heroin dependent group was significantly lower than that in the control group (p=0.017). In the genetic association analysis, we found that AA homozygotes of rs6943555 were significantly over-represented in the heroin dependent subjects compared with the control subjects (odds ratio=1.7, 95% confidence interval: 1.08-2.74, p=0.017). Analyzing the sample from the AUTS2 transcript experiment, we found that AA carriers (n=19) had significantly lower AUTS2 mRNA levels in their LCL compared to TT carriers (n=97, p=0.002) and AT carriers (n=91, p=0.005).
Conclusions:
Our data indicate that the AUTS2 gene might be associated with heroin dependence, and reduced AUTS2 gene expression might confer increased susceptibility to heroin dependence.
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