By dividing individuals with autism spectrum disorders (ASD) into four subtypes according to similarity of symptoms and reanalyzing existing genome-wide genetic data on these individuals vs. controls, researchers at the George Washington University School of Medicine and Health Sciences have identified 18 novel and highly significant genetic markers for ASD.
In addition, ten of the variants were associated with more than one ASD subtype, providing partial replication of these genetic markers. This study thus identifies candidate genes for ASD and potential subtype-dependent genetic markers for diagnostic screening. These findings, published in the April 27 edition of the journal PLoS ONE, demonstrate the increased statistical power to identify significant genetic variants when the heterogeneity of the samples tested is reduced by subtyping and further begin to associate genotype with phenotype.
"By working to tease apart the heterogeneity associated with varying severity of autistic symptoms exhibited by individuals with ASD and examining the resulting subtypes of ASD, we believe that we will continue to make strides in figuring out the genetic contributions to autism," said Valerie Hu, Ph.D., professor of Biochemistry and Molecular Biology at GW's School of Medicine and Health Sciences. "The goal of our research is to identify SNPs associated with a subtype of ASD that rise above the 'noise' of the hundreds of thousands of other SNPs when compared against controls, with the hope that we can identify genetic biomarkers for these disorders as well as clues to the biology of autism."
The researchers first identified genetic variants or single nucleotide polymorphisms (SNPs) that are associated with the degree of severity of various different autistic traits, and then they performed case-control genetic association analyses using these variants and subgroups of autistic individuals who share similar symptoms. This helped the researchers to identify the 18 genetic markers that are associated with four subtypes of ASD, ten of which were associated with more than one ASD subtype. They then examined the minor allele frequencies of the shared SNPs in the respective ASD subtypes and found that the odds ratio is different for each shared SNP, further suggesting genetic heterogeneity among the subtypes. The study also found that all of the novel variants were located in nonexonic DNA regions that do not code for protein and further identified two SNPs that are associated with differentially expressed genes from an earlier study by Dr. Hu's laboratory, suggesting a possible functional relationship between the SNPs and gene expression levels. Based on these findings, the researchers hypothesized that perhaps the newly identified genetic variants are affecting gene regulatory processes, rather than causing a change in protein structure.
Citation: Hu VW, Addington A, Hyman A (2011) Novel Autism Subtype-Dependent Genetic Variants Are Revealed by Quantitative Trait and Subphenotype Association Analyses of Published GWAS Data. PLoS ONE 6(4): e19067. doi:10.1371/journal.pone.0019067
PLEASE LINK TO THE SCIENTIFIC ARTICLE IN ONLINE VERSIONS OF YOUR REPORT (URL goes live after the embargo ends): http://dx.plos.org/10.1371/journal.pone.0019067
About The George Washington University Medical Center
The George Washington University Medical Center is an internationally recognized interdisciplinary academic health center that has conducted scientific research and provided high-quality medical care in the Washington, D.C., metropolitan area since 1824. For more information about the GW Medical Center, visit: www.gwumc.edu
www.gwumc.edu | EurekAlert!
At last, butterflies get a bigger, better evolutionary tree
16.02.2018 | Florida Museum of Natural History
New treatment strategies for chronic kidney disease from the animal kingdom
16.02.2018 | Veterinärmedizinische Universität Wien
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.
But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...
Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.
The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...
Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters
Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...
Let’s say the armrest is broken in your vintage car. As things stand, you would need a lot of luck and persistence to find the right spare part. But in the world of Industrie 4.0 and production with batch sizes of one, you can simply scan the armrest and print it out. This is made possible by the first ever 3D scanner capable of working autonomously and in real time. The autonomous scanning system will be on display at the Hannover Messe Preview on February 6 and at the Hannover Messe proper from April 23 to 27, 2018 (Hall 6, Booth A30).
Part of the charm of vintage cars is that they stopped making them long ago, so it is special when you do see one out on the roads. If something breaks or...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
16.02.2018 | Information Technology
16.02.2018 | Health and Medicine
16.02.2018 | Physics and Astronomy