Large, Multiethnic Study Identifies New Genetic Markers that Predispose People for Lupus

Large, Multiethnic Study Identifies New Genetic Markers that Predispose People for Lupus

A study of more than 27,000 people of different ethnic origins revealed 24 new genetic markers that predispose for systemic lupus erythematosus, the most common type of lupus. People with more of the predisposing genetic markers are more likely to develop the autoimmune disease, the study found.

In collaboration with Genetech, the international team of researchers published the results in the article, “Transancestral mapping and genetic load in systemic lupus erythematosus,” which appeared in the journal Nature Communications this month.

Researchers looked at the genomes of 27,574 people in three ethnic categories: European, African American, and Hispanic Amerindian ancestry. They used a Genentech technology called the Immunochip,  a system to identify the sequence of DNA regions that code for proteins of the immune system and can identify genetic markers (gene mutations and other kinds of genetic variations) associated with auto-immune diseases.

This is one of the largest studies of its kind to look at predisposing markers for systemic lupus erythematosus in African American and Hispanic Amerindian populations, where the  chronic inflammatory disease is two to three times more common in women than it is in the European ancestry population.

In the African American group, researchers analyzed DNA from 2,970 cases of systemic lupus erythematosus and 2,452 controls. The study also included DNA from 6,748 cases of the autoimmune disease and 11,516 controls in the European ancestry group, and 1,872 cases of the disease and 2,016 controls in the Hispanic Amerindian group.

The results came up with 58 genetic markers that contribute to the heritability of systemic lupus erythematosus, 24 of which were previously unidentified. Among the genetic markers, nine were specifically related to causing the disease in the African American population, while 16 others were associated with it specifically in the Hispanic Amerindian population.

Some of the markers were associated with systemic lupus erythematosus (SLE) in all of the ethnicities studied, and also with other autoimmune diseases.

“SLE has a strong genetic contribution to risk with ancestry-dependent and ancestry-independent contributions. SLE risk has shared and independent genetic contributions relative to other autoimmune diseases,” the researchers noted.

“Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE,” the study concluded.

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