Johnson Emma C, Chang Yoonhoo, Agrawal Arpana
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO.
Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO.
Curr Genet Med Rep. 2020 Jun;8(2):35-46. doi: 10.1007/s40142-020-00184-w. Epub 2020 Mar 17.
Sample size increases have resulted in novel and replicable loci for substance use disorders (SUDs). We summarize some of the latest insights into SUD genetics and discuss some next steps in addiction genetics.
Genome-wide association studies have substantiated the role of previously known variants (e.g., rs1229984 in for alcohol) and identified several novel loci for alcohol, tobacco, cannabis, opioid and cocaine use disorders. SUDs are genetically correlated with psychiatric outcomes, while liability to substance use is inconsistently associated with these outcomes and more closely associated with lifestyle factors. Specific variant associations appear to differ somewhat across populations, although similar genes and systems are implicated.
The next decade of human genetic studies of addiction should focus on expanding to non-European populations, consider pleiotropy across SUD and with other psychiatric disorders, and leverage human and cross-species functional data to elucidate the biological mechanisms underlying SUDs.
样本量的增加已产生了物质使用障碍(SUDs)的新的可重复位点。我们总结了SUD遗传学的一些最新见解,并讨论了成瘾遗传学的一些下一步措施。
全基因组关联研究证实了先前已知变异(如酒精相关的rs1229984)的作用,并确定了酒精、烟草、大麻、阿片类药物和可卡因使用障碍的几个新位点。SUDs与精神疾病结局存在遗传相关性,而物质使用易感性与这些结局的关联不一致,且与生活方式因素的关联更为密切。尽管涉及相似的基因和系统,但特定变异关联在不同人群中似乎存在一定差异。
成瘾的人类遗传学研究的下一个十年应侧重于扩展到非欧洲人群,考虑SUDs之间以及与其他精神疾病的多效性,并利用人类和跨物种功能数据来阐明SUDs的生物学机制。