SPARK: Accelerating Autism Research Together

J. Kiely Law, MD, MPH

Director of Research Operations, SPARK
Simons Foundation Autism Research Initiative
 Autism basics

• Core symptoms: 1) Deficits in social

communication, and 2) presence of restricted
interests and repetitive behaviors
• 1 in 54 children diagnosed; Boys 4 times more than
girls
• ~8 million individuals with ASD in the US
• Tremendous heterogeneity in severity and
symptoms
• Increased risk of other medical and mental health
conditions (e.g., intellectual disability, seizures,
ADHD, depression and others)
• Limited evidence-based treatments and
therapies

 What we know about the genetics of ASD: twin studies

Identical Twins Fraternal Twins Siblings General Population 1%

77% 31% 20%

How much of autism is genetic?

•Genetics factors play a large role

in ASD (50% – 80%)
•Large population study (2017)*
- 3.5 million children in Sweden
- Born between 1982 – 2006
- Genetic contribution to ASD = 83%

•Environmental Factors

•Combined interactions

*Sandin et al. 2017

Why is genetic research important?

SFARI and the evolution of genetic research in ASD

• SFARI launched in 2003 to improve the

understanding, diagnosis and treatment of ASD
by funding innovative research of the highest
quality and relevance

• Flagship autism research cohorts:

• The Simons Simplex Collection: a permanent
repository of genetic samples from 2,600 simplex
families
• Simons Searchlight: cohorts of individuals sharing
specific genetic variants known to increase the risk of
ASD and other DD (i.e., 16p11.2)

What are the challenges in ASD research?

• Tremendous variability in ASD
symptoms, severity and co-
occurring conditions
• 80% genetic, but extremely complex
and many genes involved
• Need LOTS of families to
understand the full spectrum
• Recruitment is challenging
• Strong need for reproducible
clinical research
• Need evidenced based
treatments, therapies, and
services

What is SPARK?

• Largest autism research study

ever, launched nationally in April
2016
• Aim is to better understand
genetics & biology of ASD and to
advance the development of
effective treatments & therapies
 How is SPARK accelerating autism research?

• Engaging a growing community of

individuals with ASD and their families
• Collecting medical, behavioral, &
genetic data which is analyzed by top
scientists
• Matching participants with new
research studies covering a broad range
of topics
• Returning individual genetic and
phenotypic results
 Engaging community stakeholders

Members of the autism community are

actively engaged on all advisory boards
and committees

“Being a part of the SPARK Community Advisory

Council is one way that I give a voice to my non-verbal
son and to my daughter, who also has autism. SPARK
research is the key to helping families like mine and I
am proud to be a participant.”
-Michelle Lopez

Engaging the community: Diversity and representation

• Historically, Black/African American children and

Hispanic children were under-identified as
having ASD; recent data suggests this is
improving
• Disparities in treatment access and quality care
still exist
• Communities of color are underrepresented in
health research, including autism research
• SPARK is committed to engaging all
communities
• Established DEI Advisory Board
• Launching Spanish SPARK in 2022
• Expanding local outreach efforts through
community & academic partnerships

Eligibility to join

Families and individuals with autism are eligible to join SPARK

if they:
• Live in the United States
The entire autism • Can read and understand English (and soon – Spanish!)
community is invited
to join! • Are an independent adult with ASD, or the parent of a child or
dependent adult with ASD. Biological siblings are welcome too
• Have a professional diagnosis of autism

National and local outreach

SPARK Clinical Site Network Digital and Traditional Media

 SPARK enrollment and participation process

@ https://sparkforautism.org/
* Complete surveys on your Dashboard!

Participation continues over time

Complete
Receive
surveys Individual
Reports

Participation
Join over time leads
SPARK to greater
understanding
of ASD across
the lifespan
DNA Sequencing Receive Genetic
Provide Results
saliva (~10%)
sample

Re-analysis
every year

Returning genetic results & individual reports

How does receiving a genetic diagnosis help families & individuals?
10% of SPARK participants with ASD have a genetic result

Genomic analysis of 9,751 people

with ASD
2%
8%

No returnable result
Novel returnable result
Known returnable result

90%
 Most results are in single genes and occur de novo

Result type inherited recessive & hemizygous

Inheritance
3%
aneuploidy/UPD
4%
Unknown
8%

CNV Inherited
38% SNV/Indel 24%
de novo
58% 64%

• Aneuploidy/UPD = changes at the chromosome level

• CNV (copy number variant) = single or multiple genes with greater or fewer copies
• SNV/Indel (Single nucleotide variations or insertion/deletion) = small changes in single
genes

SPARK gene list

• Genes, CNVs and chromosomal

differences must have strong and
consistent evidence that they are
associated with autism to be returned

• SPARK medical genetics committee

meets 4 times a year to discuss newly
discovered variants and whether they
should be added to the list

Autistic adult who received a genetic result

Family who received a genetic result for their son’s autism

SPARK identified and returned a genetic finding

in CHD8 gene linked to autism.

“Finding out that it was genetic, and that there was

nothing that I could have done to cause or prevent
it, was a big relief.”

“Another reason I was relieved when I got the

results back was that I learned that we’re not alone.
There are other people with the same genetic
condition.”

Simons Searchlight

• Gene-first approach to
understanding rare
neurodevelopmental
disorders

• Eligibility is based on having a

known genetic variant (full list
is available on the website)

Research Match: Connecting families with other research opportunities

4 1
Receive summary Hear about other
report of study research studies
results

3 2
Study data leads to Decide if you want
new findings to participate
 Early impact of COVID-19 on families

• Over 75% reported major disruptions in most

ASD services, with younger children experiencing
more disruptions
• Access to remote services was limited, fewer
than 50% receiving such services at follow-up one
month later
• The majority of parents reported little to no
benefit from remote services
• 64% reported moderate/severe negative impact
on child’s ASD symptoms, behaviors and challenges
due to disruptions in services and therapies
• 50% of families were “near” or “in crisis”
indicating possible need for additional resources
and supports

White et al, 2021

Adolescents with ASD – motivations for camouflaging

• “Camouflaging” is a set of strategies used by

autistic individuals to hide their autistic traits
• Many studies have examined camouflaging
in autistic adults, but very few have looked at
the experiences of adolescents
• Researchers surveyed and interviewed
adolescent participants in SPARK and their
neurotypical peers
• Camouflaging was reported in both
groups, but the motivations differed
• Autistic teen males camouflage for
“acceptance”
• Autistic teen females camouflage to
“avoid negative experiences”

Bernardin et al, 2021

Physical health symptoms in autistic young adults

• Autistic adults, ages 18-26, reported on
physical symptoms experienced in the last
3 months
• Physical symptoms are more common in
young autistic adults compared to previous
studies of the general population
• Sleep problems and fatigue were the most
common symptoms reported by males and
females
• All symptoms increased with age
• Females reported more physical health
problems than males
• Future research is needed to explore links
between physical symptoms, medical and
psychiatric conditions, & health care
utilization in the autistic population

Williams et al, 2022

Estimating the prevalence and genetic risk

mechanisms of ARFID in a large autism cohort
• Goal: Estimate prevalence of ARFID in people with autism
and whether it can be inherited
• Avoidant/Restrictive Food Intake Disorder (ARFID), first
included in the DSM-IV in 2013, is a feeding disorder
involving a pattern of food avoidance, leaving individuals
unable to meet their nutritional needs
• Very picky eating, fear of new foods, avoiding foods for
sensory reasons
• Lack of distorted body image
• Participants were administered the nine item ARFID
screen + questions about feeding and GI issues
• Study estimates risk of ARFID in individuals with autism at
21% of probands and up to 17% of their parents
• Demonstrated heritability, estimated at 0.45 (95% CI:
0.13-0.76)
• Potential genetic association of ARFID with gene ZSWIM6
and implicated several other genes, pending larger sample
size to confirm
Sharing evidence-based information
The first five years of SPARK
New research findings
• Over 50+ publications using SPARK data and research match
What does the future hold for SPARK?
• We are here for decades to come
• Big data approach to autism research and discovery
• Lifespan research
• Transition to adulthood research
• Research that reflects the diversity of the autism community
• Discover more about autism genetics and subtypes to fuel
evidence-based “precision” treatments and therapies
• Invitations to take part in all types of research through
Research Match
Join SPARK today!
It’s simple and it’s free.

SPARKforAutism.org
Thank
you!