Publications

Date Revised: October 2024

Thank you to all the families for participating in Simons Searchlight. Through your involvement, we aim to assist researchers and geneticists worldwide in understanding genetic disorders affecting you or your family.

The research conducted using Simons Searchlight data has resulted in numerous published papers. These papers undergo a peer-review process, where other scientists assess and validate the research before publication in scientific journals. Additionally, some findings are shared via preprints, allowing rapid dissemination of information to the scientific community.

Many of the publications feature the name “Simons Variation in Individuals Project” (SimonsVIP), which was the original name of our research program, now known as Simons Searchlight.

The listed articles are organized chronologically, from oldest to newest. You can explore publications by specific genetic conditions using the categories below.

As of October 2024, Simons Searchlight has contributed to 108 publications and preprints, and we will continue to summarize new publications.

For accessibility, the Simons Foundation encourages researchers to make their publications open access. If you cannot access a journal article, we recommend reaching out to the last author listed on the paper to request a copy.

Understanding Publication Reference Titles:

-The article title is followed by publication details, including where and when it was published.
– If there are more than three authors, we use “et al.” to represent additional contributors.
– Journals are referenced using shorthand names.

Disclaimer: Please be aware that papers posted on medRxiv (pronounced med-archive) or bioRxiv (pronounced bio-archive) are not peer-reviewed or edited before online publication. In contrast, all other articles listed here have undergone review by fellow researchers to ensure quality and accuracy. While posting on medRxiv or bioRxiv allows researchers to share findings quickly, the final published results may differ after undergoing formal peer review for journal publication.

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Genetic Condition
Year of Publication
108 Publications
Quantifying the effects of 16p11.2 copy number variants on brain structure: A multisite genetic-first study
  • Previous studies described the brain structure differences in people with 16p11.2 deletions or duplications. This research study aimed to measure the difference as a quantity.Show More
  • Magnetic resonance imaging (MRI) was conducted in Simons Searchlight participants, and of 16p11.2 participants in a study in Europe. The study included 78 people with a 16p11.2 deletion, 71 people with a 16p11.2 duplication, and 212 people without a deletion or duplication.
  • This publication included the list of psychiatric diagnoses for each group of people. This includes autism, ADHD, and motor disorder.
  • This study found similar brain patterns as other MRI studies. Brain regions affected by a 16p11.2 deletion or duplication were involved in language, making sounds, working memory, flexible thinking, and self-control. The diagnosis of different psychiatric conditions was not related to any specific brain structures.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Biol Psychiatry 84, 253-264 (2018)
Martin-Brevet et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2018

The psychiatric phenotypes of 1q21 distal deletion and duplication
  • A copy number variant (CNV) happens when there is a change in a section of DNA that results in a gene or several genes being deleted or duplicated. 1q21 deletion is an example of a CNV.Show More
  • Researchers studied the largest number of people to date with a 1q21 CNV. This included 51 children with a 1q21 deletion, 44 children with a 1q21 duplication, 17 adults with a 1q21 deletion, and 11 adults with a 1q21 duplication. There were 28 children and 32 adults included who did not have a genetic condition.
  • Participants with a 1q21 CNV were included from three different international, in-person studies: Simons Searchlight, CNV Research Group at Lausanne University Hospital, and Neuroscience and Mental Health Research Institute at Cardiff University.
  • Children with a duplication or deletion were more likely to have a neurodevelopmental condition like autism, ADHD, and intellectual disability than children without the genetic condition.
  • The researchers found that anxiety was common in participants with a deletion or duplication.
  • Participants with a 1q21 deletion tended to have a smaller head size than participants with a 1q21 duplication.
  • The researchers suggested that smaller studies of people with a 1q21 deletion or duplication did not give accurate rates of certain mental health diagnoses. They found that there was no evidence of a link to certain psychiatric syndromes, unlike what has been described in other papers.
  • The IQ of participants with a 1q21 deletion or duplication varied widely, but it was usually lower than the IQ of participants without the genetic condition. This was true for everyone except adults with a 1q21 duplication.
  • This research was supported by a grant from the Simons Foundation Autism Research Initiative (SFARI).Show Less
Transl Psychiatry 11, 105 (2018)
Linden et al.
Full Article

1q21.1 deletion
1q21.1 duplication
2018

Patterns of delay in early gross motor and expressive language milestone attainment in probands with genetic conditions versus idiopathic ASD from SFARI registries
  • These researchers studied when motor and language milestones were reached for children with genetic conditions associated with neurodevelopmental disorders, as compared with people with autism and people with no genetic diagnosis.Show More
  • Motor milestones included learning to sit, crawl, or walk. Language milestones included developing single words and combinations of words.
  • Children with autism usually develop motor milestones within a typical timeframe, whereas people with autism reach their language milestones over a varied timeframe.
  • This is the first study that looked at a multi-gene, cross-comparison in Simons Searchlight participants.
  • The researchers studied 16 genetic conditions and data in Simons Searchlight: 1q21.1 deletion, 1q21.1 duplication, 16p11.2 deletion, 16p11.2 duplication, ADNP, ASXL3, CSNK2A1, DYRK1A, GRIN2B, MED13L, PACS1, PPP2R5D, SCN2A, SLC6A1, STXBP1, and SYNGAP1. This study included 479 participants with a genetic diagnosis.
  • The researchers compared the group of people with a genetic diagnosis to 3,506 SPARK participants who underwent genetic testing but did not have a genetic diagnosis. Like Simons Searchlight, SPARK is another study funded by the Simons Foundation. People who participate in SPARK have an autism diagnosis.
  • For the group of people with a genetic diagnosis, 1 in 3 had an autism diagnosis, 1 in 4 had intellectual disability, and 1 in 3 had seizures. For the group of people with autism, 1 in 10 had intellectual disability, and 1 in 25 had seizures. This paper includes a table that shows each genetic condition and the age at which each milestone was reached.
  • The group with a genetic diagnosis was more delayed in reaching their motor and language milestones than participants with autism. But, participants with autism also had delayed language milestones.
  • Eight of the genetic conditions (ADNP, ASXL3, GRIN2B, MED13L, PACS1, PPP2R5D, STXBP1, and SYNGAP1) had delays for all milestones in at least half of participants.
  • The researchers suggested that motor delays of six months or never reaching the milestone were an indicator of a genetic condition, whereas speech delays were not specific to these genetic conditions.Show Less
J Child Psychol Psychiatry 62, 1297-1307 (2018)
Wickstrom et al.
Full Article

16p11.2 deletion
16p11.2 duplication
1q21.1 deletion
1q21.1 duplication
ADNP
ASXL3
CSNK2A1
DYRK1A
GRIN2B
MED13L
PACS1
PPP2R5D
SCN2A
SLC6A1
STXBP1
SYNGAP1
2018

Haplotype-specific MAPK3 expression in 16p11.2 deletion contributes to variable neurodevelopment
  • These researchers studied clinical and genetic information from different people to learn which genes within the 16p11.2 region might play an important role in development.Show More
  • This study included 31 children with a 16p11.2 deletion, as well as induced pluripotent stem cells (iPSCs) made from human participants. iPSCs are a special type of cells that can be turned into other body cells, making it easier to study parts of the body that are difficult to study, such as brain cells.
  • This study also included a group of people from China. These participants had a 16p11.2 deletion. The researchers compared the findings from this group with the Simons Searchlight data.
  • The researchers created a haplotype. This means that they studied the pattern of genes that were included in participants with a 16p11.2 deletion and autism, to see if they could find genes that might be needed for brain function. There are about 29 genes included in the typical 16p11.2 deletion region, but not every person who has the deletion is missing the same genes (see image below). The breakpoints can be different for different people and include more or fewer genes.
  • The researchers turned the iPSCs into brain cells and looked to see what genes were expressed. Checking for gene expression is one way to know whether the gene is being used by the cell. Different cell types express different genes.
  • The researchers found that the MAPK3 gene was a major contributor to brain cell development. MAPK3 stands for mitogen-activated protein kinase 3, and it is an enzyme needed for cell communication.
  • This study focused on the role of MAPK3 in gene expression and human brain cell development. The findings suggest that medical features that are caused by a 16p11.2 deletion are not only due to a MAPK3, but are also due to other genes in the region.Show Less
Brain Epub ahead of print, (2018)
Liu et al.
Full Article

16p11.2 deletion
2018

Cellular phenotypes in human iPSC-derived neurons from a genetic model of autism spectrum disorder
  • To make 16p11.2 deletion neurons (brain cells) to study, skin samples were donated from 3 people with 16p11.2 deletions and 3 with 16p11.2 duplications in Simons Searchlight. Show More
  • Induced pluripotent stem cells (iPSCs) were created from the skin cells and then turned into neurons.
  • Researchers found that the 16p11.2 deletion neuron size and shape was different from neurons with no deletion.
  • Neurons with 16p11.2 deletions were bigger and longer but 16p11.2 duplication neurons were smaller and shorter.
  • Researchers think that this might explain why people with 16p11.2 deletions have larger brain sizes and people with 16p11.2 duplications have smaller brain sizes.
  • Both 16p11.2 deletion and duplication neurons had fewer connections (synapses) between their neurons develop, which the researchers think might explain how behaviors are similar in people with 16p11.2 deletions and duplications. Show Less
Cell Rep 21, 2678-2687 (2017)
Deshpande et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2017

Maternal modifiers and parent-of-origin bias of the autism-associated 16p11.2 CNV
  • 459 individuals from 126 families enrolled in Simons Searchlight with a 16p11.2 deletion or duplication underwent genetic analysis to see if there is a difference if inherited from the mother or father.Show More
  • 79 people with non-inherited 16p11.2 deletions or duplications had the genetic change occur on the maternally-inherited copy in most cases (9 out of 10 times).
  • This maternal tendency was not observed for 16p11.2 deletions or duplications that were inherited.
  • These finding suggest that non-inherited 16p11.2 deletions or duplications are due to an increase in genetic material swapping (recombination) during female egg cell formation.
  • Similarly, in this study, about 8 out of 10 people with other genetic deletions were found to be either non-inherited or from their mothers.
  • While more genetic deletions only mildly affected a person’s IQ, they were related to more severe overall clinical features.
  • Researchers suggest that understanding of the variation of clinical features in people with 16p11.2 requires full genetic sequencing.Show Less
Am J Hum Genet 98, 45-57 (2016)
Duyzend et al.
Full Article

16p11.2 deletion
16p11.2 duplication
2016

Defining the effect of the 16p11.2 duplication on cognition, behavior, and medical comorbidities
  • To gain a better understanding of the clinical features people with 16p11.2 deletions and duplications may have, researchers studied the largest group of people to date. This included 1006 people, 270 16p11.2 duplication carriers, 390 deletion carriers, and 346 relatives. Show More
  • Data was collected from three studies, 1) Simons Searchlight, 2) the 16p11.2 European Consortium and 3) the Cardiff University Experiences of Children With Copy Number Variants.
  • Results found that the frequency of ASD diagnoses and IQ issues were similar for 16p11.2 deletions and duplications.
  • However, 16p11.2 duplications exhibit a range of IQ deficits from mild to severe, while 16p11.2 deletions exhibit overall moderate IQ deficits.
  • Both deletion and duplication carriers have delays in learning to walk, yet duplication carriers are more likely to have more delays of over 2 years.
  • Finally, people with 16p11.2 duplications had a 2.5 times increase in the presence of additional deletions or duplications in other regions of their DNA. This suggests that the extra or missing pieces of other genetic information might contribute to the clinical features of people with a 16p11.2 duplication. Show Less
JAMA Psychiatry 73, 20-30 (2016)
D'Angelo et al.
Full Article

16p11.2 duplication
2016