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In addition to systemic and organ\u2010specific inflammation, patients may display features of immunodeficiency or allergy, which may represent major diagnostic and therapeutic challenges. The person's genetic architecture has been a well\u2010established risk factor for patients with RDs, albeit to variable degrees. Patients with early\u2010onset diseases and\/or positive family history (FH) have a strong genetic component, whereas patients with late\u2010onset RDs demonstrate a more complex interplay of genetic and environmental risk factors. Overall, the genetic studies in patients with RDs have been instrumental to our understanding of innate and adaptive immunity in human health and disease. The elucidation of the molecular causes underlying rare diseases has played a major role in the identification of genes that are critical in the regulation of inflammatory responses. In addition, studies of patients with rare disorders may help determine the mechanisms of more complex autoimmune diseases by identifying variants with small effect sizes in the same genes. In contrast, studies of patients with common RDs are conducted in cohorts of patients with well\u2010established phenotypes and ancestry\u2010matched controls, and they aim to discover disease\u2010related pathways that can inform the development of novel targeted therapies. Knowing the genetic cause of a disease has helped patients and families understand the disease progression and outcome. Here, we discuss the current understanding of genetic heritability and challenges in the diagnosis of RDs in patients and how this field may develop in the future.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42841-toc-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1002\/art.42841","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T04:01:30Z","timestamp":1709524890000},"page":"1169-1181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Approaches to Study Rheumatic Diseases and Its Implications in Clinical 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