Biological Psych：精神分裂症风险基因和大麻依赖风险相关

刊登在国际杂志Biological Psychiatry上的一篇研究报告中，研究者揭示了基因NRG1或涉及对大麻依赖的风险。基因NRG1编码ErbB4受体，该受体是突触发育和功能维持的重要蛋白质。

研究者对大麻依赖的敏感基因进行了调查分析，正如研究者以前揭示的这些敏感性基因具有较强的遗传组分。文章中，研究者对非洲美国人和欧洲美国人家庭进行了一项多重研究，首先进行连锁分析，研究者在非洲美国人染色体8p21上鉴别出了最强的信号。随后研究者使用全基因组关联性分析发现了在非洲美国人和欧洲美国人身上共有的NRG1突变。最后，研究者在非洲美国人独立样品中单独复制了该突变。通过研究发现，NRG1或许是大麻依赖性的敏感基因。

在这项研究中，研究者也揭示了精神分裂症的遗传性和大麻依赖遗传性之间的关系，发现NRG1也涉及精神分裂症的遗传风险中，随后的研究表明，诊断为精神分裂症的个体，其大脑中NRG1的表达发生了改变。

当前的研究或许可以帮助揭示大麻的使用和精神分裂症发病之间的关系，一系列的流行病学研究也证实了这种关系。当前的研究数据为我们理解精神分裂症的遗传风险提供了新的视角，也有助于我们更清楚理解精神分裂症的风险基因和大麻依赖之间的关系。

与精神分裂相关的拓展阅读：

• Biological Psych：精神分裂症风险基因和大麻依赖风险相关
• Biol Psychiat：免疫系统功能底下是患精神分裂症潜在风险因素
• Pharmacol Biochem Behav：研究发现氯氮平和奥氮平抗精神分裂作用机制
• BMJ Open：精神分裂症与躯体疾病共病相关
• EPA 2013：吸食大麻与精神分裂症较严重相关
• Biol Psychiatry：TMS可改善精神分裂症患者的记忆
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Linkage Analysis Followed by Association Show NRG1 Associated with Cannabis Dependence in African Americans

Background A genetic contribution to cannabis dependence (CaD) has been established but susceptibility genes for CaD remain largely unknown. Methods We employed a multistage design to identify genetic variants underlying CaD. We first performed a genome-wide linkage scan for CaD in 384 African American (AA) and 354 European American families ascertained for genetic studies of cocaine and opioid dependence. We then conducted association analysis under the linkage peak, first using data from a genome-wide association study from the Study of Addiction: Genetics and Environment, followed by replication studies of prioritized single nucleotide polymorphisms (SNPs) in independent samples. Results We identified the strongest linkage evidence with CaD (logarithm of odds = 2.9) on chromosome 8p21.1 in AAs. In the association analysis of the Study of Addiction: Genetics and Environment sample under the linkage peak, we identified one SNP (rs17664708) associated with CaD in both AAs (odds ratio [OR] = 2.93, p = .0022) and European Americans (OR = 1.38, p = .02). This SNP, located at NRG1, a susceptibility gene for schizophrenia, was prioritized for further study. We replicated the association of rs17664708 with CaD in an independent AAs sample (OR = 2.81, p = .0068). The joint analysis of the two AA samples demonstrated highly significant association between rs17664708 and CaD with adjustment for either global (p = .00044) or local ancestry (p = .00075). Conclusions Our study shows that NRG1 is probably a susceptibility gene for CaD, based on convergent evidence of linkage and replicated associations in two independent AA samples.