Cumulative Genetic Hit Hypothesis for Lupus Save

A recent report in Nature Communications has studied multiple nationalities has shown a "disentangled complex HLA multigenic effect" underlying the genetic basis of systemic lupus erythematosus (SLE).  (Citation source: http://buff.ly/2u623Ht)

An international consortium of scientists have collaborated to identify new genetic markers that predispose individuals to lupus. Using a multiple center, investigating multi-ethnic lupus groups, they sought to identify genes specific to individual ethnic groups and others that are shared across ethnicities.

They found that many of the genetic markers associated with lupus are shared across numerous autoimmune diseases.

They analyzed genetic data from 27,574 individuals of European, African American and Hispanic ancestry using Immunochip genotyping technology designed for autoimmune diseases.

The researchers identified 58 regions of the genome in Caucasians, nine in African Americans and 16 in Hispanics. They found that nearly 50 percent of these specific regions had multiple genetic variants that predispose to lupus.

They also showed that the lupus risk allele count (or genetic load) accelerates the pattern of SLE risk. These observations led the authors to propose a "cumulative hits hypothesis for autoimmune disease".

These multi-ancestral SLE case-control samples identified 24 novel SLE-risk regions, while at the same time replicating established SLE-risk loci and extending their impact into other ancestries, and refined associated signals via transancestral mapping. 

SLE was shown to have strong genetic contribution to risk with ancestry-dependent and ancestry-independent contributions. SLE risk is genetically shared with other autoimmune diseases. .