The more I learn, the more I realize how much I don’t know.
This quote, attributed to Albert Einstein, is an apt way to begin this issue. The field of genomics seems to constantly expand and now includes genome sequence, functional and comparative genomic analyses, bioinformatics, epigenomics/epigenetics, gene expression, gene regulation (including microRNAs), and metagenomics. Concomitant with these advances, comprehending human biology through understanding the genetic material present in a cell or organism and how it works seems to become more formidable. However, through reductionist approaches, incremental gains provide optimism for better understanding of human diseases and their diagnosis, prevention, and treatment.
If one takes a “splitter” approach rather than a “lumper” approach, there are more than 100 rheumatic diseases, which include inflammatory conditions such as rheumatoid arthritis, autoimmune diseases such as systemic lupus erythematosus, metabolic diseases such as gout, and degenerative conditions such as osteoarthritis. A variety of phenotypes have been addressed using genomic approaches, including disease susceptibility, analysis of subphenotypes/clinical subsets, disease severity, treatment response (pharmacogenomics), and so forth. While genomics plays a role in almost all human diseases, much of the influence on development of rheumatic diseases is nongenetic, which encompasses environmental, lifestyle, diet, and random factors, which are exceedingly difficult to accurately measure and interpret.
In this issue, we address a selected subset of topics relevant to genomics in rheumatic diseases, in addition to the traditional discussion of associations between genes/loci and disease states. This includes focus on population genetics and natural selection; influences on disease severity and treatment response, the role of the major histocompatibility complex locus, drug repositioning strategies, and integrative approaches. Diseases that are discussed include rheumatoid arthritis, systemic lupus erythematosus, gout, ankylosing spondylitis, autoinflammatory diseases (which are typically monogenic), and juvenile idiopathic arthritis. We chose not to include several topics (scleroderma, osteoarthritis, psoriatic arthritis, inflammatory myositis, vasculitis, others) because of excellent recent reviews elsewhere in the medical literature, a paucity of high-quality data upon which to write a review, or page limitations in this issue.
Looking at recent trends in biomedical research, two underlying themes that have emerged as ways to better understand human disease seem antithetical: big data analysis (computational biology, systems biology, integrative biology, and so forth) and the emergence of single-cell technologies. While this issue does not address single-cell approaches per se, one article focuses on the use of integrative approaches to stratify pathologic genetic variants, and another focuses on the use of large datasets to identify new uses for existing drugs.
In summary, genome-based approaches can be incorporated into research designed to dissect how various elements work together to affect the human body in both health and disease. New findings help to focus on which questions to ask as well as on how to answer them. Genomics research can potentially lead to improved diagnostic tests, more effective strategies for disease management, and better decision-making tools for both health care providers and patients. We are hopeful that the question is not if, but when, we will cross the threshold of integrating results of genomics research in everyday practice of medicine.
We are very grateful to this issue’s authors, who are leaders in the field of rheumatic diseases research. Their contributions have helped to greatly advance the field, and their perspectives have resulted in outstanding, informative articles.