Bioinformatics Program, Boston University, Boston, Massachusetts.
Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, Massachusetts.
Curr Protoc. 2022 May;2(5):e426. doi: 10.1002/cpz1.426.
Mapping quantitative trait loci (QTLs) for molecular traits from chromatin to metabolites (i.e., xQTLs) provides insight into the locations and effect modes of genetic variants that influence these molecular phenotypes and the propagation of functional consequences of each variant. xQTL studies indirectly interrogate the functional landscape of the molecular basis of complex diseases, including the impact of non-coding regulatory variants, the tissue specificity of regulatory elements, and their contribution to disease by integrating with genome-wide association studies (GWAS). We summarize a variety of molecular xQTL studies in human tissues and cells. In addition, using the Alzheimer's Disease Sequencing Project (ADSP) as an example, we describe the ADSP xQTL project, a collaborative effort across the ADSP Functional Genomics Consortium (ADSP-FGC). The project's ultimate goal is a reference map of Alzheimer's-related QTLs using existing datasets from multiple omics layers to help us study the consequences of genetic variants identified in the ADSP. xQTL studies enable the identification of the causal genes and pathways in GWAS loci, which will likely aid in the discovery of novel biomarkers and therapeutic targets for complex diseases. © 2022 Wiley Periodicals LLC.
对染色质到代谢物的分子特征的数量性状基因座（QTL）进行作图（即 xQTL），可以深入了解影响这些分子表型和每种变体功能后果传播的遗传变异的位置和作用模式。xQTL 研究通过与全基因组关联研究（GWAS）相结合，间接探究复杂疾病分子基础的功能图谱，包括非编码调控变体的影响、调控元件的组织特异性及其对疾病的贡献。我们总结了人类组织和细胞中各种分子 xQTL 的研究。此外，我们以阿尔茨海默病测序项目（ADSP）为例，描述了 ADSP xQTL 项目，这是 ADSP 功能基因组学联盟（ADSP-FGC）的一项合作努力。该项目的最终目标是使用来自多个组学层面的现有数据集，为与阿尔茨海默病相关的 QTL 构建参考图谱，以帮助我们研究在 ADSP 中发现的遗传变异的后果。xQTL 研究能够确定 GWAS 基因座中的因果基因和途径，这可能有助于发现复杂疾病的新型生物标志物和治疗靶点。© 2022 威立出版社
