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Autoimmune Disease

Autoimmune Diseases and Genetic Testing

Recent advances in genetic testing, specifically genome-wide association studies (GWAS), are helping medical researchers to develop better strategies to detect, treat, and prevent autoimmune diseases.

“GWAS have been especially fruitful in the study of autoimmune disease,” wrote Simon Makin in his Nature article, “Cracking the Genetic Code of Autoimmune Disease”. “Although individual variants in the hundreds of associated loci (lists of genetic regions generated) have only a small impact on risk, they bring about significant changes at a molecular level.”

The National Human Genome Research Institute (NHGRI) says that the impact on medical care from GWAS could potentially be substantial.

“Such research is laying the groundwork for the era of personalized medicine, in which the current one-size-fits-all approach to medical care will give way to more customized strategies,” says the NHGRI. “Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease, and mental illnesses.”

80+ Autoimmune Diseases Attack the Body from Within

The National Institute of Allergy and Infectious Diseases (NIAID) says that more than 80 diseases occur because of the immune system attacking the body’s own organs, tissues, and cells.

Some of the more common autoimmune diseases include:

  • Type 1 diabetes
  • Rheumatoid arthritis
  • Systemic lupus erythematosus
  • Inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis
  • Multiple sclerosis
  • Psoriasis
  • Graves’ disease

“Imagine that your body is a castle, and your immune system is your army fighting off invaders like bacteria,” explains the Cleveland Clinic. “If your army malfunctions and attacks the castle, you may have lupus, multiple sclerosis, rheumatoid arthritis, and/or psoriasis, among a hundred other autoimmune diseases.”

The Cleveland Clinic estimates that 1 in 15 people in the U.S. has an autoimmune disease, with 1 million people with lupus and 1.4 million people with Crohn’s disease or ulcerative colitis. They also estimate that 1.24 million people in the U.S. live with Type 1 diabetes, a number expected to soar to 5 million by 2050.

“Although the causes of many autoimmune diseases remain unknown, a person’s genes in combination with infections and other environmental exposures are likely to play a significant role in disease development. Treatments are available for many autoimmune diseases, but cures have yet to be discovered,” said the NIAID.

What is a Genome-Wide Association Study (GWAS)?

A genome-wide association study (GWAS) is an approach that involves rapidly scanning markers across the complete sets of DNA, or genomes, of many people to find genetic variations associated with a particular disease.

GWAS was not possible until recently after the completion of the Human Genome Project in 2003 and the International HapMap Project in 2005.

“Researchers now have a set of research tools that make it possible to find the genetic contributions to common diseases,” said the NHGRI.

These tools include:

  • Computerized databases that contain the human genome sequence
  • A map of human genetic variation
  • Set of new technologies that can quickly and accurately analyze whole-genome samples for genetic variations that contribute to the onset of a disease

“In the future, after improvements are made in the cost and efficiency of genome-wide scans and other innovative technologies, health professionals will be able to use such tools to provide patients with individualized information about their risks of developing certain diseases,” says the NHGRI. “The information will enable health professionals to tailor prevention programs to each person's unique genetic makeup. In addition, if a patient does become ill, the information can be used to select the treatments most likely to be effective and least likely to cause adverse reactions in that particular patient.”

What Genome-Wide Association Studies Have Found

The NHGRI says that researchers have reported considerable success using this new genetic testing strategy including variation in genes associated with:

  • A common form of blindness
  • Type 2 diabetes
  • Parkinson’s disease
  • Heart disorders
  • Obesity
  • Crohn’s disease
  • Prostate cancer
  • Response to antidepressant medications

“GWAS have now implicated hundreds of regions of the genome in various autoimmune diseases,” wrote Makin. “These variants typically have small individual effects, but collectively they contribute significantly to the risk and reveal the basic biology of autoimmunity.”

Genes Suggest Autoimmune Diseases Share Underlying Traits

Researchers say that many of the genes implicated by these variants suggest that autoimmune diseases share some underlying traits centered around over-active pro-inflammatory T cells or underperforming regulatory T cells or B cells.

“One region that is linked to many autoimmune diseases, including Crohn’s disease, systemic lupus erythematosus, and psoriasis, contains the TYK2 gene,” wrote Makin. “This encodes an enzyme crucial to the function of some cytokines — signaling molecules that are central to coordinating immune responses.”

On the opposite end of common gene variation identification, are rare monogenic conditions that are caused by a variation in a single gene and are often associated with familial inheritance.

“Monogenic disorders can provide considerable insight into a disease because of their profound impact on a person’s biology. Conversely, the effects of common variants are typically much smaller,” wrote Makin.

One example cited is a rare form of lupus caused by the loss of function of a single gene called DNASE1L3. Common variants in this gene also modestly increase the risk of rheumatoid arthritis and scleroderma, as well as lupus.

Other researchers are looking into variants that are rare but instead of monogenic, cause polygenic diseases or genetic disorders that are caused by a combination of more than one gene. Examples include hypertension, coronary heart disease, and diabetes.

“For autoimmune diseases, as in some complex diseases, we believe that we will find an entire spectrum of variants: from a mix of common variants with weak effects acting together, to a few or single rare variants with strong effects causing that disease,” said Carola Vinuesa, MD, PhD, head of the Department of Immunology and Infectious Disease at the John Curtin School of Medical Research. “For some diseases, it’s becoming obvious that we will need a molecular diagnosis to know what type of treatment will be most effective.”