Genetics & Rheumatic Diseases


Many forms of rheumatic diseases, including forms of arthritis, have a genetic basis. The study of genetics focuses on how human characteristics are inherited from one’s ancestors including appearance and even risk for disease. There are approximately 20,000–25,000 genes. These genes, which are a small portion of a chromosome, are randomly passed from parents to offspring.

What Are Unifactorial and Multifactorial Diseases?

Diseases that happen due to a mutation or normal variation in genes are usually classified as either unifactorial or multifactorial. Unifactorial suggests one gene is related to the condition. Multifactorial (or polygenic) suggests multiple genes interacting with each other leads to a condition.

How Twin Studies Help

Studying twins has proven very helpful in examining the genetic and environmental influences that may cause rheumatic disease. Identical twins have exactly the same genes, while non-identical twins typically have about half of the same genes, like most siblings. If the disease is unifactorial, both identical twins nearly always will be affected, while a much smaller percentage of non-identical twins will both develop the disease. In multifactorial diseases, the frequency of both identical twins getting the disease is 5–70%, and for non-identical pairs, even lower.

Genetics and Ankylosing Spondylitis

Each rheumatic disease has its own cause(s), including a certain genetic background. One of the strongest examples of this genetic influence on a rheumatic disease is the connection between ankylosing spondylitis (AS) and a gene called HLA-B27.

More than 90% of Caucasian AS patients have the HLA-B27 gene, compared to the approximately 7% of the general population who carry this gene. This means only a small portion of the general population (approximately 5%) who carries the gene will develop the disease.

On the other hand, first-degree family members (parents, siblings and children) of AS patients with the HLA-B27 gene have a 20 percent chance of developing the disease.

Genetics and Rheumatoid Arthritis

Rheumatoid arthritis, a multifactorial disease, occurs in approximately 1% of the population worldwide. The gene link with rheumatoid arthritis is to an immune system gene called HLA-DR4. In rheumatoid arthritis patients of European ancestry, as many as 60–70% carry the HLA-DR4 gene, compared with 30% in the general population.

Twin studies indicate that genes only slightly increase the risk for rheumatoid arthritis and that environmental factors are likely to play a stronger role.

Genetics and Autoimmune Diseases

Frequently, multiple, and different autoimmune diseases are observed in the same families. Recent technological advances have enabled a more comprehensive examination of the genetic basis of rheumatic diseases.

Updated April 2023 by Mohammad Ursani, MD, and reviewed by the American College of Rheumatology Communications and Marketing Committee.

This patient fact sheet is provided for general education only. Individuals should consult a qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition.

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