Genetics of substance use disorders: a review.
Genetics of substance use disorders: a review.
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DOI：
10.1017/s0033291721000969
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发表时间：
2021-10
影响因子：
6.9
通讯作者：
Johnson EC
中科院分区：
文献类型：
--
作者：
Deak JD;Johnson EC
物质使用障碍（SUD）很普遍，并导致一系列负面后果。它们受遗传因素的影响（h2 = ~50%）。近年来，我们对SUD的遗传病因学和相关性状的理解取得了实质性进展。本综述涵盖了SUD遗传学领域的现状，包括SUD的流行病学和遗传流行病学，第一代SUD全基因组关联研究（GWAS）的发现，将GWAS研究结果转化为临床环境的注意事项，并建议下一波SUD遗传学工作的优先顺序。SUD遗传学的最新进展已经通过大GWAS样品的组装以及对全基因组变异的聚集效应进行建模的最先进方法的发展而得到促进。这些进展已经证实SUD是高度多基因的，在整个基因组中具有赋予风险的许多变体，其中绝大多数影响很小。下游分析使SUD的遗传结构的更精细的分辨率，并揭示了他们与其他精神疾病的遗传关系的见解。最近的努力也优先考虑更仔细地检查GWAS的发现，这些发现表明，在物质使用（例如消费）和有问题的使用（例如SUD）的措施中存在不一致的遗传影响。最近SUD GWAS的其他亮点包括酒精代谢基因（如ADH 1B和ALDH 2）中影响酒精相关性状的位点的有力确认，以及CHRNA 5-CHRNA 3-CHRNB 4基因簇中影响尼古丁相关性状的位点。预计大麻、阿片类药物和可卡因使用障碍也会取得类似的成功，因为样本量接近酒精和尼古丁的样本量。
Substance use disorders (SUDs) are prevalent and result in an array of negative consequences. They are influenced by genetic factors (h2 = ~50%). Recent years have brought substantial progress in our understanding of the genetic etiology of SUDs and related traits. The present review covers the current state of the field for SUD genetics, including the epidemiology and genetic epidemiology of SUDs, findings from the first-generation of SUD genome-wide association studies (GWAS), cautions about translating GWAS findings to clinical settings, and suggested prioritizations for the next wave of SUD genetics efforts. Recent advances in SUD genetics have been facilitated by the assembly of large GWAS samples, and the development of state-of-the-art methods modeling the aggregate effect of genome-wide variation. These advances have confirmed that SUDs are highly polygenic with many variants across the genome conferring risk, the vast majority of which are of small effect. Downstream analyses have enabled finer resolution of the genetic architecture of SUDs and revealed insights into their genetic relationship with other psychiatric disorders. Recent efforts have also prioritized a closer examination of GWAS findings that have suggested non-uniform genetic influences across measures of substance use (e.g. consumption) and problematic use (e.g. SUD). Additional highlights from recent SUD GWAS include the robust confirmation of loci in alcohol metabolizing genes (e.g. ADH1B and ALDH2) affecting alcohol-related traits, and loci within the CHRNA5-CHRNA3-CHRNB4 gene cluster influencing nicotine-related traits. Similar successes are expected for cannabis, opioid, and cocaine use disorders as sample sizes approach those assembled for alcohol and nicotine.