Identifying the Role of Rare and Low-Frequency Variants in Complex Diseases and Traits: Utilization of Third-Generation Sequencing and Construction of Polygenic Risk Scores

The contribution of rare and low-frequency variants to complex traits and diseases has been explored in genetics research. These variants have puzzled scientists in missing heritability problems for many years. With the development of biotechnology, sequencing technology has emerged as a tool for exploring biological and medical research questions, especially the third-generation long-read sequencing. It is now possible to more accurately identify rare and low-frequency variants, and even rare, low-frequency structural variants and haplotypes. Rare and low-frequency variants have undergone purifying selection throughout history. However, it remains unclear how these variants have played roles in complex traits and diseases. Constructing a model of polygenic risk scores, particularly including the contribution of rare and low-frequency variants, will aid in genetic risk prediction for personalized medicine.

Through this research topic, we intend to shed more light on advancements in genomic sequencing and its role in understanding and managing complex diseases. Original Research articles and Reviews are welcome, including but not limited to the following contents:

• The identification of causal variants and haplotypes using third-generation long-read sequencing.

• The contribution of rare and low-frequency variants to complex traits and diseases.

• The construction of polygenic risk scores that include rare and low-frequency variants.

Keywords: Rare and low-frequency variants, Complex disease, Complex trait

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.