NIDA CENTER FOR GENETIC STUDIES. MARCH 14, 2022 - MARCH 13, 2023. N01DA-18-7797. TASK ORDER 75N95022F00001 (TO8).

物质使用障碍（SUD）包括一大类复杂的表型，构成了一个重大的公共卫生挑战。SUD的病因包括遗传和环境因素，阻碍了基于遗传的治疗靶点的鉴定、验证、复制和功能评估。然而，新的技术和科学突破带来了巨大的希望，可以梳理出与SUD相关的潜在遗传和表观遗传特征，包括单核苷酸多态性（SNP），染色质相互作用，基因表达差异，罕见变异，拷贝数变异，功能性SNP，indels和大型染色体重排。这些技术进步，沿着新兴的方法来测量环境暴露和产生人类重编程细胞衍生物，有可能增加我们对SUD病因的理解，并加速新的治疗化合物和预测/诊断测试的开发。

Substance use disorders (SUD) comprise a broad category of complex phenotypes that constitute a major public health challenge. The etiology of SUD encompasses genetic and environmental components, hampering the identification, validation, replication, and functional assessment of genetic-based therapeutic targets. However, new technological and scientific breakthroughs hold tremendous promise to tease out the underlying genetic and epigenetic signatures associated with SUD, including single nucleotide polymorphisms (SNPs), chromatin interactions, gene expression differences, rare variants, copy number variants, functional SNPs, indels and large chromosomal rearrangements. These technological advances, along with emerging methods to measure environmental exposures and generate human reprogrammed cellular derivatives, have the potential to increase our understanding of the etiology of SUD and accelerate the development of new therapeutic compounds and predictive/diagnostic tests.