Why Is It Important To Know If You Have A Family Health History Of Autism Spectrum Disorder
Having a family health history of ASD makes you more likely to have a child with ASD, or to have ASD yourself. If you have a child with ASD, you are more likely to have another child with ASDexternal icon, especially if you have a daughter with ASD or more than one child with ASDexternal icon. Your other family members would also be more likely to have a child with ASD.
If you are pregnant or planning a pregnancy, tell your doctor if you or your partner have a family health history of ASD. This information can help your doctor determine how likely you are to have a child with ASD.
When collecting family health history information,
- Include your and your partners children, parents, sisters, brothers, grandparents, aunts, uncles, nieces, and nephews;
- Include anyone with a diagnosis of ASDexternal icon, learning disorder, intellectual disability, schizophreniaexternal icon, epilepsy/seizures, personality disorderexternal icon, or attention-deficit/hyperactivity disorder ;
- Note if anyone had genetic testing and the results of that testing;
- Include anyone with a genetic disorder that can cause ASD, such as fragile X syndrome or Rett syndromeexternal icon;
- Be sure to include anyone who received a diagnosis that is no longer used, such as Asperger syndrome or mental retardation; and
- Consider including older family members who have or had signs of ASD, even if they were not diagnosed with ASD, as ASD diagnoses were less common in the past and might have been missed.
Linkage Disequilibrium Score Regression Analysis
LD SCore regression , was used to estimate genome-wide SNP based heritability, heritability enrichment of tissue/cell-type specific epigenetic states, and genetic correlation across phenotypes for GWAS meta-analysis results . Prior to the analyses, we filtered SNPs to those found in HapMap3 and converted to LDSC input files using munge_sumstats.py. The pre-computed LD scores for Europeans were obtained from https://data.broadinstitute.org/alkesgroup/LDSCORE/eur_w_ld_chr.tar.bz2. For all LDSC analyses, we used individuals from European ancestry as described in the Genome-wide association analysis section above.
Symbols Preceding Mim Numbers
Symbols preceding MIM numbers indicate the entry category:
- An asterisk before an entry number indicates a gene.
- A number symbol before an entry number indicates that it is a descriptive entry, usually of a phenotype, and does not represent a unique locus. The reason for the use of the number symbol is given in the first paragraph of the entry. Discussion of any gene related to the phenotype resides in another entry as described in the first paragraph.
- A plus sign before an entry number indicates that the entry contains the description of a gene of known sequence and a phenotype.
- A percent sign before an entry number indicates that the entry describes a confirmed Mendelian phenotype or phenotypic locus for which the underlying molecular basis is not known.
- No symbol before an entry number generally indicates a description of a phenotype for which the Mendelian basis, although suspected, has not been clearly established or that the separateness of this phenotype from that in another entry is unclear.
- A before an entry number means the entry no longer exists because it was removed from the database or moved to another entry as indicated.
Is Autism Genetic Study Finds 80% Risk From Inherited Genes
September 6, 2019
A new study looking at autism in 5 countries found that 80 percent of autism risk can be traced to inherited genes rather than environmental factors and random mutations.
The study, published July 18 in JAMA Psychiatry, analyzed data of nearly 2 million people across Denmark, Finland, Sweden, Israel, and Western Australia. It is the largest family-based genetic autism study to date, including children with autism, their siblings and cousins, as well as parents and their siblings.
We expanded on previous results by including more family members and data from countries that vary widely in their autism health systems, said Joseph Buxbaum, M.D., one of the study authors and professor of psychiatry at the Icahn School of Medicine at Mt. Sinai Medical Center. We found that the strongest contributors to risk of autism are from inherited genes. Spontaneous genetic changes and other factors that we could not estimate are additional contributors to risk of autism.
In addition, the study found very little or no risk resulting from maternal effects such as chronic health conditions that are consistent across all of a womans pregnancies. But for maternal factors that might occur in only one pregnancy, the studys analysis cant separate out those risks.
While the studys authors concluded that maternal effects create no risk for autism, researchers who study these effects say this is a complicated issue.
Autism Largely Caused By Genetics Not Environment: Study
WEDNESDAY, July 17, 2019 — The largest study of its kind, involving more than 2 million people across five countries, finds that autism spectrum disorders are 80% reliant on inherited genes.
That means that environmental causes are responsible for just 20% of the risk.
The findings could open new doors to research into the genetic causes of autism, which the U.S. Centers for Disease Control and Prevention now says affects 1 in every 59 U.S. children.
It might also help ease fears that autism is caused by maternal factors — a mother’s weight, mode or timing of delivery, or nutrient intake, for example. The new study found the role of maternal factors to be “nonexistent or minimal.”
Instead, “the current study results provide the strongest evidence to our knowledge to date that the majority of risk for autism spectrum disorders is from genetic factors,” said a team led by Sven Sandin, an epidemiological researcher at the Karolinska Institute in Stockholm, Sweden.
The new study might help dampen public interest in supposed — but unproven — “environmental” causes of autism, such as vaccines. Long-discredited, fraudulent data linking childhood vaccination with autism is still widely cited by the “anti-vaxxer” movement.
They noted the new numbers are roughly in line with those from prior, smaller studies on the issue, further bolstering their validity.
Plenty Of Genes Involved
Some genetic conditions are simple, and they stem from one unusual item found in one strand of DNA. Autism is much different, and that complexity makes the condition a lot harder to spot.
In January 2020, researchers published the results of a massive study that included:
- A large study group. More than 35,000 people sent in samples for analysis.
- ASD data. Of the 35,000 participants, almost 12,000 had autism spectrum disorder.
- Gene sequencing. Testing methods picked up rare mutations that might stay masked with other methods.
Per the results, more than 102 genes were attached to autism risk. This is a huge number, and researchers suspect that the genes intertwine and intermingle.
Some of them are associated with other developmental delays. Others seem to increase the risk of neurodevelopmental disorders.
The researchers don’t yet know how the genes work, so parents can’t walk into a laboratory and ask for an autism gene screening. There is too much data to look for and a lot we don’t know.
But this study suggests that many genes, working together, could raise autism risks. That data could be helpful as researchers look for ways to treat, and perhaps even cure, ASD.
What Is The Treatment For Autism
There is currently no cure for autism. However, autism can be managed and shaped at a young age, even as early as pre-school. Early intensive therapy can have a positive effect on development later in life.
Treatment of autism involves medical and behavioral therapies to help children with conversational language and social interactions. Treatment also involves helping children decrease their repetitive, self-stimulatory behaviors, tantrums and self-injurious behavior.
Medications can help treat specific symptoms such as aggressive or self-injurious behavior, inattention, poor sleep and repetitive behaviors. However, no medications are autism specific and medications should be used in conjunction with a family-centered, behavioral and educational program.
How Is Autism Diagnosed
Diagnosis of autism is based on standardized testing plus a clinical evaluation by an autism specialist. These professionals are usually psychologists, psychiatrists, developmental pediatricians, pediatric neurologists or medical geneticists.
The diagnosis of autism is made when there are a specific number of symptoms as defined by the Diagnostic and Standard Manual of Mental Disorders . Some commonly used diagnostic tests are the CARS , the ABC and the GARS . Formal diagnosis by an autism specialist usually depends on completing the ADOS , and ADI-R . The CHAT is often used in pediatrician’s offices to screen for autism symptoms.
When physical features, small head size or brain malformations are present or there is a family history of relatives with autism, genetic testing such as chromosome analysis and single-gene testing is done.
Autism Is A Complex Genetic Disorder
First-degree relatives of ASD probands have an increase in behavioral or cognitive features associated with autism, such as social or language dysfunction, albeit in lesser forms, when compared with the population prevalence . This has been called the broader phenotype and includes restrictive repetitive behaviors and sub-threshold deficits in social cognition, as well as language dysfunction . For example, language delay is observed in a significant proportion of non-autistic siblings of autistic probands . Similarly, autistic-like social impairment clearly is heritable and increased in unaffected parents and children of autistic probands . Studies using multiple measures of sub-threshold autistic traits in population cohorts suggest that different components, separately representing language, social function and repetitive or stereotyped behaviors contribute to ASD . On aggregate, these data suggest that different features of autism represent a quantitative continuum of function that may be inherited in distinct patterns. This is consistent with the knowledge that specific genetic factors contribute to the development and function of specific brain structures, and that distinct brain circuits may underlie different components of autism .
Autism Has A Genetic Component
Autism is hereditary, in that children with autistic people in their family are more likely than other children to be autistic. Researchers are well on the way to finding genes that relate to autism — but the jury is still out regarding exactly how such genes might function to create autistic symptoms. Sophia Colamarino, Science Program Director at Cure Autism Now, explains, “Were talking about genes because they allow us to understand the biological origins of the problem.”
There Is A Relationship Between Autism And Brain Structure
Recent brain studies show that autistic brains grow at an unusual rate between the ages one and two and then slow again to a normal rate of growth. Some imaging studies suggest that certain areas of the brain are larger than is typical. Research is ongoing to determine whether these differences in brain structure cause autism, are caused by autism, or are comorbid with autism and caused by something else.
What Are The Symptoms Of Autism
Autism usually develops before 3 years of age and affects each individual differently and to varying degrees. It ranges in severity from relatively mild social and communicative impairments to a severe disability requiring lifelong parental, school and societal support.
The hallmark symptom of autism is impaired social interaction. Children with autism may fail to respond to their name and often avoid eye contact with other people. They have difficulty interpreting what others are thinking or feeling because they don’t understand social cues provided by tone of voice or facial expressions and they don’t watch other people’s faces to pick up on these cues.
Many children with autism engage in repetitive movements such as rocking, spinning, twirling or jumping, or in self-abusive behavior such as hand biting or head-banging.
Of children being diagnosed now with an autism spectrum disorder, about half will have intellectual disabilities defined by nonverbal IQ testing, and 25 percent will also develop seizures. Though most children show signs of autism in the first year of life, about 30 percent will seem fine and then regress in both their language and social interactions at around 18 months of age.
About 30 percent of children with autism have physical signs of some alteration in early development such as physical features that differ from their parents , small head size or structural brain malformations.
Gwas In Spark Dataset Identified A New Locus Associated With Asd Risk
Fig. 1: Genome-wide association of ASD in the SPARK dataset.
a GWAS result from SPARK full dataset . b Genetic correlations across ASD GWAS. From left to right, iPSYCH versus PGC, SPARK EUR versus iPSYCH, SPARK EUR versus PGC and SPARK EUR versus iPSYCH-PGC study. c GWAS results from the meta-analysis . For Manhattan plots , the x-axes indicate the chromosomal position and y-axes indicate the significance of associations. The blue and red lines denote the significance threshold at suggestive and significant levels. SNPs with P<1×106 are shown as a filled circle. Rs number indicates index SNPs from independent loci at P<1×108). Index SNPs at P<5×108 are shown as diamonds. d Common variant risk burden is higher in cases compared to pseudocontrols. e Comparison of PRS across family types , multiple affected children with unaffected parents, one affected child with affected parent, and one affected child with unaffected parents) shows no evidence for a higher common variant burden in multiplex families. f Comparison of PRS between male and female probands shows no evidence of enrichment of common variants impacting risk for ASD in females. g There is no evidence for a difference in the transmission of common variant risk burden from mother versus father.
What We Can Do While We Search For Answers
Clearly, it will take time for us to elucidate the role that genetics play in causing or exacerbating autism. Even then, the answers will not be simple, because different genes and different environmental factors will be at play in different people. Fortunately, however, there are steps we can take right now to aid individuals with autismespecially if their symptoms may stem in whole or in part from genetic vulnerability. In particular, there are four areas in which we can focus our efforts:
Nutrition. It is becoming clear that many individuals with autism have nutritional deficiencies, and that some of these may be caused or worsened by genetic vulnerabilities . In-depth testing of individuals with autism can help to uncover any existing nutritional deficiencies and allow us to address them effectivelywhether the causes are genetic or not.
Toxins. Reducing the body burden of toxins in individuals with autism will benefit all of them, but especially those with genetic vulnerabilities that make them more prone to damage from these toxins. In addition to addressing major sources of pollution at the government and industry level, we can take personal action by minimizing the use of toxic chemicals in our own homes.
Early intervention. While genetic anomalies may underlie the behaviors and learning problems of many individuals with autism, we now know that early intervention can dramatically benefit children with ASD no matter what the cause.
Stephen M. Edelson, Ph.D.
Diagnostic Models Based On Imaging Genetics
Imaging genetics in ASD has proven useful, and pathways that include common genetic variation in TD individuals at risk of developing ASD have been characterized. Prenatal transcription regulation and synapse formation in the developing brain is impacted by the genes associated with ASD . Alteration in frontal WM connectivity and structure and disturbance in the frontal, temporal, and occipital circuits involved in visual and language processing was found to be associated with NRXN superfamily genes. Neuropeptide signaling and emotional functioning was found to be influenced by the oxytocin and arginine vasopressin receptor genes via structural and functional modification in the amygdalahypothalamus circuitry. One study showed a relationship between frontal lobe connectivity and common genetic variants in CNTNAP2 using a functional neuroimaging study and the study found that ASD and TD individuals who were nonrisk allele carriers showed more reduction in the activation of mPFC during an fMRI task as compared to risk allele carriers. Another study showed decreased functional connectivity in the prefrontal cortex, cortical spinal tract, corpus callosum, and decreased integrity of WM in children and adolescents carrying MET rs1858830, C risk allele. Such studies suggest that the genes affect the brain regions that are involved in social and emotional processing.
Genetic Testing For Autism Spectrum Disorder
In todays world, unfortunately, there is no genetic testing to detect autism spectrum disorder before birth, when the baby is in the womb.
We need to know that autism spectrum disorder is first and foremost a genetic disorder. Most of the risk of autism comes from genes. Mutation in genes causes this condition. While there are four types of tests that can detect these mutations, there is no definite specific test that can diagnose autism.
Genetic tests used to detect other genetic disorders in the womb cannot be used to diagnose autism. Because environmental factors are involved in autism and a situation after the test can change the result. It does not mean that there are hundreds of mutations that lead to this situation, but not every gene mutated causes autism.
Lets say the genetic test was applied and you got a negative result. But after your baby was born and raised, you learned that he had autism. This is a very livable scenario. The genetic tests in question may not be receiving a particular mutation, or there is no relationship with autism at the time of the test. For this reason, most genetic testing facilities reanaly the results once a year based on the latest findings.
Clinical Implications And Future Perspectives
When autism was first described, it was hypothesized to be an environmentally caused disease. Decades of research have since revealed that autism is a highly heterogeneous and extremely complex genetic condition. Even though great progress had been made in identifying hundreds of risk genes, very little is known about the different types of modifiers that may exacerbate or ameliorate disease severity. Such modifiers could include epigenetics, sex-linked modifiers, CNVs, double-hit mutations, or environmental factors .
Figure 1. Genetic modifiers in autism spectrum disorder. Autism is estimated to be 4080% heritable. However, both genetic and non-genetic factors modulate the penetrance of risk genes, resulting in a highly heterogeneous disease phenotype for similar pathogenic variants. Examples of genetic modulators include CNV, epigenetics, and double-hit mutations. Examples of non-genetic modifiers include environmental exposures and sex-linked modifiers.
What Can Families Do Right Now
Your family doctor can’t offer you gene splicing. Some can’t even provide genetic counseling. If you have autism and you are considering having kids, know that your children may have the same condition you do. If you don’t have autism but someone in your family does, the risks may still be enhanced for your child.
If you have a child or loved one with autism, watch the results of studies. Talk over questions with your doctor. Look for ways to support charities that fund autism research. The more we know about this disease, the better.
The Role Of Rare Mutations Versus Common Polymorphisms In Asd
A series of important findings over the last four years clearly challenges the notion that autism is mainly caused by combinations of common variants by identifying a large number of rare, recurrent, and non-recurrent mutations that lead to ASD. At the same time, whole genome association studies with common variants, while identifying a few loci with very small effect sizes, have not yielded independently replicated results . These rare mutations, mostly in the form of sub-microscopic chromosomal structural variation, called copy number variants , are now known to account for up to 10% of cases of idiopathic autism . Since many of these CNV have large effect sizes and thus are thought sufficient to cause ASD, they are predicted to significantly reduce reproductive fitness. Consistent with this, these causal CNV are often not transmitted from the parent, but instead occur de novo in the germline . However, in some cases, such as CNV at 16p11 and 15q11-13, the CNV are transmitted from an unaffected parent to cause the disorder in an offspring . The genetic or epigenetic mechanism for the reduced penetrance for ASD in the mutation-carrying parent is not known. However, it is also very likely that the parent carriers of such CNV have more subtle neuropsychiatric or cognitive phenotypes that have not yet been systematically identified.
What Might The Doctor Recommend For Your Child If You Have A Family Health History Of Autism Spectrum Disorder
Knowing about your family health history of ASD can help your childs doctor better care for your child. The doctor may check your child more closely for early signs of ASD and might refer your child to a specialist for further evaluation. When a child is closely monitored, signs of ASD can sometimes be noticed at 18 months or youngerexternal icon. A reliable diagnosis of ASD is more common around 2 or 3 years of ageexternal icon and usually made by a developmental specialist. If a child is diagnosed at a young age with ASD, treatment is more effective. Also, a diagnosis of ASD is important for tailoring childrens education once they start school. Learn how early intervention leads to better outcomes for children with ASD.
If you are pregnant or planning a pregnancy, your doctor might recommend carrier screening if you have a family health history of a genetic disorder, such as fragile X syndrome.
Evidence For Converging Molecular Pathways
Several recent studies have suggested that in addition to convergent brain pathways, that there may as well be convergence at the level of molecular mechanisms in ASD. One class of such studies has asked whether putative ASD susceptibility genes are enriched in members for specific molecular or biological processes more than expected by chance. The value of this approach depends on the level of experimental support for the specific genes tested and the degree to which current pathway annotations represent reality . For genes identified within CNV this can be particularly problematic, as most known pathological CNV contain more than one gene and it is not expected that all genes within the CNV contribute to ASD, potentially increasing noise in this analysis. One recent study reduced such background by using a new phenotype-driven method to group genes within high confidence de novo CNV , identifying significant enrichment for several categories of genes, including axon outgrowth, synaptogenesis, cell-cell adhesion, GTPase signaling, and the actin cytoskeleton. These results replicate and extend earlier composite pathway analysis of putative ASD susceptibility genes compiled from the literature , and CNV pathway analysis in the Autism Genetic Resource Exchange and other cohorts . Still, these studies place ASD genes within a multiplicity of pathways, several of which are broad and do not necessarily demonstrate convergence on final common molecular processes in individuals.
Early Diagnosis Is Critical
Frazier emphasized that formal autism diagnosis can open the door to certain treatments.
He also said that children with specific developmental delays like speech or motor issues should be referred for services immediately without waiting for an autism diagnosis.
This ensures that children can continue to make progress and develop early skills that help them reach their full potential, he said.
The School Bus Problem
Why do American high schools generally start so early? One large part of the answer: school buses. A lot of school districts re-use the same buses to pick up students from different schools: first the high schoolers, then the middle schoolers, and finally the elementary schoolers. In South Carolina, the order is generally reversed, which is why it is among the “latest” states on this map.
Early school starts are not the only cause of teenage drowsiness, but they are a crucial factor especially because natural sleep cycles make it difficult for post-puberty teenagers to fall asleep before 11 pm.
A poll by the National Sleep Foundation found that 59 percent of 6th through 8th graders and 87 percent of high school students got less than the recommended amount of sleep on school nights. In the words of America’s leading soporific publication Sleep Review, the average American adolescent is “chronically sleep-deprived and pathologically sleepy”.
Chronic sleep loss in adolescents has been linked to a host of negative consequences:
Because of all those reasons, not just the AAP but also the CDC recommends later school start times and urges parents to advocate for them. Fortunately, this has met some success. In 2019, California Governor Gavin Newsom signed into law Bill 328, which requires middle schools to begin no earlier than 8:00 am and high schools no earlier than 8:30 am. It will go into effect in 2022.