DHAKA, Bangladesh
A new national collaboration of asthma genetics researchers has revealed a novel gene associated with thedisease in African-Americans, according to a new scientific report. By pooling data from nine independent research groups looking forgenes associated with asthma, the newly-created EVE Consortiumidentified a novel gene association specific to populations ofAfrican descent. In addition, the new study confirmed thesignificance of four gene associations recently reported by aEuropean asthma genetics study. The findings, published in Nature Genetics, are a promising first step for a new national scientific effort tohunt for the genetic roots of asthma. "We now have a really good handle on at least five genes thatanyone would be comfortable saying are asthma risk loci," saidCarole Ober, PhD, co-chair of the EVE Consortium, senior author ofthe study, and Blum-Riese Professor of human genetics andobstetrics/gynecology at the University of Chicago.
"I think it'san exciting time in asthma genetics." "Asthma rates have been on the rise in recent years, with thegreatest rise among African Americans," said Susan B. Shurin, M.D.,acting director of the National Heart, Lung, and Blood Institute(NHLBI) of the National Institutes of Health, which co-funded thestudy. "Understanding these genetic links is an important firststep towards our goal of relieving the increased burden of asthmain this population." Genome-wide association studies, or GWAS, are a popular method usedby geneticists to find genetic variants associated with elevatedrisk for a particular disease. Genetic data from a group ofpatients with the target disease are compared to data from acontrol group without the disease, and researchers look forvariants that appear significantly more often in the disease group. But the ability, or power, of GWAS to find disease-associatedvariants is dependent on the number of participants enrolled in astudy.
To find variants involved in complex diseases, thousands ofparticipants may be necessary - a logistical and financial demandoften beyond the capacity of an individual research team. "It has become clear to geneticists studying nearly every commondisease that GWAS are often under-powered, and unless you pulltogether many researchers doing the same thing you're just notgoing to have the power to find genes," said Dan Nicolae, PhD,associate professor of medicine, statistics, and human genetics atUniversity of Chicago, co-chair of the consortium and anothersenior author of the study. "That was the motivation for ninegroups of investigators coming together to form EVE." Spurred by support from the NHLBI and the National Institutes ofHealth, research groups from the nine institutions discussedpooling their GWAS data to create a larger, shared dataset. But itwasn't until they received a $5.6 million grant from the AmericanRecovery and Reinvestment Act of 2009 that the EVE Consortium couldofficially form and hire the necessary personnel to execute thecollaboration. Co2 Fractional Laser Machine
"It would never have been possible without the grant, this was ahuge amount of work," said Nicolae, "The key was the ARRA fundingthat allowed us to move it faster." In addition to increased power to find variants associated withasthma risk, the EVE dataset comprised a more ethnically diversepopulation than similar efforts in other countries by includingEuropean Americans, African Americans/African Caribbeans, andLatinos. "We believe that this heterogeneity is important," Ober said."There are differences in asthma prevalence in these three groups,so it's important to understand whether these are caused byenvironmental exposures or by differences in genetic risk factors." The diverse sample enabled the researchers to discover a novelgenetic association with asthma observed exclusively inAfrican-Americans and African-Caribbeans. The polymorphism, locatedin a gene called PYHIN1, was not present in European-Americans andmay be the first asthma susceptibility gene variant specific topopulations of African descent. Four more gene variants were found significant for asthma risk bythe meta-analysis: the 17q21 locus, and IL1RL1, TSLP, and IL33genes. All four of these sites were concurrently identified in aseparate dataset by the GABRIEL Study of more than 40,000 Europeanasthma cases published last year in the New England Journal ofMedicine. China PDT Led Machine
Confirming these associations in the more diverse EVEpopulation offers additional evidence that the gene variants aresignificant across ethnicities, the researchers reported. "We were able to show that almost all of the genes other thanPYHIN1 are trans-ethnic and important in all of the groups," Obersaid. The Nature Genetics study is only the first fruit of the EVE Consortium mission tounderstand the genetics of asthma. A deeper meta-analysis lookingat a longer list of gene variants is currently underway, andindividual groups within the consortium are using the pooleddataset to answer additional questions. Topics of interest includegene-environment interactions, genetic associations withasthma-associated phenotypes such as allergies and lung function,and the role of tissue-specific gene expression. Co2 Laser Machines Manufacturer
"What you see here in this paper is only the beginning," Nicolaesaid. "The foundation was to make people work together, share thedata, and share research ideas, and that will generate a lot ofresearch down the road." Notes: In addition to Ober and Nicolae, lead investigators of groupsparticipating in the consortium include W. James Gauderman andFrank D. Gilliand of University of Southern California; Eugene R.Bleecker and Deborah A. Meyers of Wake Forest University; BenjaminA.
Raby and Scott T. Weiss of Harvard Medical School; Stephanie J.London of the National Institute of Environmental Health Sciences;Esteban G. Burchard of University of California, San Francisco;Fernando D. Martinez of University of Arizona; L.
Keoki Williams ofHenry Ford Health System; and Kathleen C. Barnes of Johns HopkinsUniversity. Additional References Citations.
"I think it'san exciting time in asthma genetics." "Asthma rates have been on the rise in recent years, with thegreatest rise among African Americans," said Susan B. Shurin, M.D.,acting director of the National Heart, Lung, and Blood Institute(NHLBI) of the National Institutes of Health, which co-funded thestudy. "Understanding these genetic links is an important firststep towards our goal of relieving the increased burden of asthmain this population." Genome-wide association studies, or GWAS, are a popular method usedby geneticists to find genetic variants associated with elevatedrisk for a particular disease. Genetic data from a group ofpatients with the target disease are compared to data from acontrol group without the disease, and researchers look forvariants that appear significantly more often in the disease group. But the ability, or power, of GWAS to find disease-associatedvariants is dependent on the number of participants enrolled in astudy.
To find variants involved in complex diseases, thousands ofparticipants may be necessary - a logistical and financial demandoften beyond the capacity of an individual research team. "It has become clear to geneticists studying nearly every commondisease that GWAS are often under-powered, and unless you pulltogether many researchers doing the same thing you're just notgoing to have the power to find genes," said Dan Nicolae, PhD,associate professor of medicine, statistics, and human genetics atUniversity of Chicago, co-chair of the consortium and anothersenior author of the study. "That was the motivation for ninegroups of investigators coming together to form EVE." Spurred by support from the NHLBI and the National Institutes ofHealth, research groups from the nine institutions discussedpooling their GWAS data to create a larger, shared dataset. But itwasn't until they received a $5.6 million grant from the AmericanRecovery and Reinvestment Act of 2009 that the EVE Consortium couldofficially form and hire the necessary personnel to execute thecollaboration. Co2 Fractional Laser Machine
"It would never have been possible without the grant, this was ahuge amount of work," said Nicolae, "The key was the ARRA fundingthat allowed us to move it faster." In addition to increased power to find variants associated withasthma risk, the EVE dataset comprised a more ethnically diversepopulation than similar efforts in other countries by includingEuropean Americans, African Americans/African Caribbeans, andLatinos. "We believe that this heterogeneity is important," Ober said."There are differences in asthma prevalence in these three groups,so it's important to understand whether these are caused byenvironmental exposures or by differences in genetic risk factors." The diverse sample enabled the researchers to discover a novelgenetic association with asthma observed exclusively inAfrican-Americans and African-Caribbeans. The polymorphism, locatedin a gene called PYHIN1, was not present in European-Americans andmay be the first asthma susceptibility gene variant specific topopulations of African descent. Four more gene variants were found significant for asthma risk bythe meta-analysis: the 17q21 locus, and IL1RL1, TSLP, and IL33genes. All four of these sites were concurrently identified in aseparate dataset by the GABRIEL Study of more than 40,000 Europeanasthma cases published last year in the New England Journal ofMedicine. China PDT Led Machine
Confirming these associations in the more diverse EVEpopulation offers additional evidence that the gene variants aresignificant across ethnicities, the researchers reported. "We were able to show that almost all of the genes other thanPYHIN1 are trans-ethnic and important in all of the groups," Obersaid. The Nature Genetics study is only the first fruit of the EVE Consortium mission tounderstand the genetics of asthma. A deeper meta-analysis lookingat a longer list of gene variants is currently underway, andindividual groups within the consortium are using the pooleddataset to answer additional questions. Topics of interest includegene-environment interactions, genetic associations withasthma-associated phenotypes such as allergies and lung function,and the role of tissue-specific gene expression. Co2 Laser Machines Manufacturer
"What you see here in this paper is only the beginning," Nicolaesaid. "The foundation was to make people work together, share thedata, and share research ideas, and that will generate a lot ofresearch down the road." Notes: In addition to Ober and Nicolae, lead investigators of groupsparticipating in the consortium include W. James Gauderman andFrank D. Gilliand of University of Southern California; Eugene R.Bleecker and Deborah A. Meyers of Wake Forest University; BenjaminA.
Raby and Scott T. Weiss of Harvard Medical School; Stephanie J.London of the National Institute of Environmental Health Sciences;Esteban G. Burchard of University of California, San Francisco;Fernando D. Martinez of University of Arizona; L.
Keoki Williams ofHenry Ford Health System; and Kathleen C. Barnes of Johns HopkinsUniversity. Additional References Citations.