18 novel subtype-dependent genetic variants for autism spectrum disorders revealed
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.
More information: 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
Provided by George Washington University Medical Center
- Autism susceptibility genes identified Mar 25, 2010 | not rated yet | 0
- Brain scans detect autism's signature Nov 15, 2010 | not rated yet | 0
- Genetic links to impaired social behavior in autism May 13, 2008 | not rated yet | 0
- Study finds evidence of gender bias toward diagnosing boys with autism Nov 17, 2010 | not rated yet | 0
- Genetic finding identifies male-linked mutation associated with autism spectrum disorders Sep 15, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
Genetics 23 hours ago | 3 / 5 (2) | 0 |
Can human genes be patented? That was the question posed by Alan J. Snyder, vice president and associate provost for research and graduate studies at Lehigh, and Lee Kaplan, scientific director of cellular and molecular genetics ...
Genetics May 24, 2013 | 4 / 5 (1) | 0
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics May 22, 2013 | 4.5 / 5 (4) | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
7 hours ago | 5 / 5 (2) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
7 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
7 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
7 hours ago | not rated yet | 0
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
23 hours ago | not rated yet | 1