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New Consortium to Study Link Between Rare Disorders, Psychiatric Conditions

Published on March 31, 2020 · Last updated 1 year ago


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The Genome to Mental Health consortium will be analyzing the link between rare genomic disorders and psychiatric conditions, including autism.

shafere1 [at] (By Emily Shafer)

Researchers at Children’s Hospital of Philadelphia are collaborating with 13 other institutions worldwide to bridge existing gaps in understanding of brain and behavior by studying the role of rare genomic disorders in behavioral and cognitive symptoms.

The new Genome to Mental Health consortium is a $6 million initiative involving four projects funded by the National Institute of Mental Health (NIMH) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Donna McDonald-McGinn, MS, LCGC, director of the 22q and You Center at CHOP, chief of the Section of Genetic Counseling, and associate director of the Clinical Genetics Center, will lead the work to be contributed from the CHOP site.

Rare genomic disorders are a common cause of psychiatric and developmental conditions, such as autism spectrum disorder, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD). For example, 22q11.2 deletion affects only about one in 2,000 people in the general population; however, it is the second most common cause of developmental delay, after Down syndrome, and it is also the most common cause of schizophrenia.

“This project is funded to not only examine the chromosome 22q11.2 deletion, but also 22q11.2 duplication, which is highly associated with autism, and other copy number variants, such as 16p11.2 deletion and duplication” said McDonald-McGinn, who is also a clinical professor of Pediatrics at the Perelman School of Medicine of the University of Pennsylvania. “These conditions are the result of extra or missing pieces of chromosomes, leading to extra or missing copies of genes and resulting in behavioral differences.”

McDonald-McGinn and her colleagues will begin by focusing on a subset of patients who participated in a five-year study as part of the International 22q11.2 Brain and Behavior consortium (IBBC). In that study, funded by NIMH in 2012, researchers from 22 clinical and five genomic sites worldwide examined clinical and genomic data from patients with 22q11.2 deletion, both with and without psychiatric illness. They used the data to identify risk factors for psychiatric disease, with hopes of identifying early modifiers and better treatment strategies. This new study, will allow Prof. McDonald-McGinn and colleagues to expand upon that data and compare clinical and genomic findings across several chromosomal differences.

“We’re performing very detailed cognitive and behavioral batteries to understand the behavioral differences in individuals with chromosomal deletions and duplications, known as copy number variants or CNVs,” McDonald-McGinn said. “Concurrently, we are performing whole genome sequencing to examine the overall genetic background in those individuals with CNVs, to consider not only the effect of the area we know to be involved, eg, the 22q11.2 deletion, but to also identify changes elsewhere in the genome for potential modifiers of the behavioral phenotypes.”

Most rare genomic disorders have been studied separately in small studies, and as a result, most of the information about these diseases is challenging to compare. The consortium enables researchers to cross-analyze the data from several collaborative studies and harmonize the evaluations, complementing each other’s work.

The Genome to Mental Health researchers will be examining multiple phenotypes, including psychosis, anxiety, ADHD, depression, and autism, to determine their prevalence and to identify specific genes within the copy number variants that may contribute to how patients present and how the longitudinal disease course will progress.

“We are pooling our resources and working as a network to speed things along, in the hope that the greater number of participants the better insight we’ll have - both from the patient and investigator perspective,” McDonald-McGinn said.

Ultimately, the researchers conducting these studies, funded by this initiative, aim to inform early detection of these conditions and their associated features, as well as, identify biologic targets that could someday be used to develop novel therapeutics for these patients.