A variant of a gene called PYTHIN 1 that is missing in European Americans has been identified by US Geneticists, and this new gene is exclusively associated with Asthma in African Americans. A European study published last year demonstrated the existence of 4 other “trans-ethnic” genes, which was further confirmed by the new national collaboration. A national endeavor to establish the genetic roots of asthma has been furthered in a new study published in the July 31 online issue of Nature Genetics.
The study researchers belong to a newly created EVE consortium comprising scientists from 9 different groups who decided to team up, join forces, and pool data after realizing that the search for new genes by individual research teams is quite a cumbersome task.
Blum-Riese Professor of human genetics and obstetrics/gynecology at the University of Chicago, chairperson of the EVE Consortium, and senior author, Dr. Carole Ober, spoke to the media saying that it is an “exciting time in asthma genetics.”
She added: “We now have a really good handle on at least five genes that anyone would be comfortable saying are asthma risk loci. We were able to show that almost all of the genes other than PYHIN1 are trans-ethnic and important in all of the groups.”
The EVE Consortium was confronted with a challenge of how to enhance the power of genome-wide association studies (GWAS). GWAS are well-liked by scientists who are on the look-out for gene variants associated with a greater risk of certain diseases. Genetic data from a diseased group of patients are compared with a non-diseased control group in order to identify frequently occurring variants in the diseased group. Nevertheless, the power of GWAS, while searching for complex disease variants, seems inadequate in the absence of data from thousands of participants. This is a logistical and financial challenge that cannot be accomplished often using resources of individual research teams. Hence, collaborative resource sharing by teams becomes significant with genetics studies using GWAS.
Senior author of the study and associate professor of medicine, statistics, and human genetics at University of Chicago, Dr. Dan Nicolae, is a co-chairperson at the EVE Consortium. He said that more and more geneticists who are using GWAS to study diseases are realizing that “unless you pull together many researchers doing the same thing you’re just not going to have the power to find genes.”
He explained: “That was the motivation for nine groups of investigators coming together to form EVE.”
Although the research groups were contemplating the idea of forming a Consortium for quite some time, they lacked the most vital component: finance. Since these projects are massively expensive, the teams could join forces and start recruiting employees only after having received a $5.6 million grant from the American Recovery and Reinvestment Act (ARRA) of 2009. The Consortium was also backed by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institutes of Health.
Nicolae said that it would have been impossible without the grant: “The key was the ARRA funding that allowed us to move it faster.”
Comprising a data set from an ethnically diverse population is another key component to raise the power of GWAS to a level that is required to locate variants associated with asthma risk. Something that studies from other countries were not able to accomplish thus far is that when the groups teamed up to form the EVE Consortium, they brought with them certain data that when pooled together included European Americans, African Americans/African Caribbeans, and Latinos.
Ober, who said: “We believe that this heterogeneity is important,” went on to explain that: “There are differences in asthma prevalence in these three groups, so it’s important to understand whether these are caused by environmental exposures or by differences in genetic risk factors.”
In recent years, Asthma has been on the rise, particularly among African Americans, in the US.
The researchers of this study employed GWAS of asthma to collate data from 5,416 asthma individuals who were of European American, African American or African Caribbean, and Latino ancestry, followed by its simulation in another 12,649 individuals of the same ethnic groups.
A total of five variants or “susceptibility loci” (one on the 17q21 gene, and three near the genes IL1RL1, TSLP and IL33) were found by researchers. GABRIEL Study researchers, who had studied 40,000 European asthma cases and published their findings in the New England Journal of Medicine last year, had previously identified these variants in a separate data set.
However, on having the benefit of working with diverse ethnic populations, the EVE researchers were able fish-out a remarkable piece of information about these four variants, as they write in their paper: “we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups.”
They also found a “new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent.” European-Americans failed to have this polymorphism.
“These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma,” concluded the EVE researchers.
Encouraged by these discoveries and findings, the EVE Consortium is all set to discover more about the genetics of asthma by extensively exploring the data. They desire to investigate gene-environment interactions, links with allergies and lung function, and the role of tissue-specific gene expression.
Nicolae said that this paper is just the beginning, and it has laid the foundation to make the researchers work together and share ideas “that will generate a lot of research down the road.”