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NIMH to Award up to $16M for Mental Disorder Genome Collaborations

NEW YORK (GenomeWeb News) – The National Institute of Mental Health plans to provide up to $4 million per year to fund efforts that use whole-genome sequencing to uncover the genomic basis for severe mental disorders, such as schizophrenia and bipolar disorder, among others.

NIMH will support a consortium of collaborative research projects for up to four years to generate and analyze whole genome sequence data with the aim of providing insights into the "genetic architecture underlying susceptibility to severe mental disorders," according to a NIMH funding opportunity document posted today.

Whole-genome sequencing presents a unique opportunity for studying severe mental disorders, NIMH Genomics Research Branch Chief Thomas Lehner told GenomeWeb Daily News today.

Lehner said this project is akin to the recently-launched PsychEncode project; both are examples of NIMH's ambitions to help "delineate the genetic architecture of mental disorders across all levels of analysis."

"This is an effort to follow through on our understanding of the complexity of the genetic architecture of mental disorders," he added.

These types of disorders have high heritability, estimated at around 80 percent, but as with many other human disorders they are complex and may be influenced by a number of genes and environmental factors.

Many robust and replicable genetic findings have been reported for psychiatric disorders over the past few years, with most of them coming from genome-wide association and structural variation studies, but these findings have failed to explain much of the estimated heritability, which has been termed the "missing heritability problem," according to NIMH.

There is no comprehensive picture of the genomic architecture for any psychiatric disorder, and more data is needed about the specific loci involved in these disorders, NIMH said.

The projects funded under this program, "Unveiling the Genome: Genetic Architecture of Severe Mental Disorders Revealed," will aim to map out parts of this architecture. They will use existing cohorts and samples, like those available through the NIMH repository, to produce whole-genome sequence data and conduct analyses to identify the genomic contributions to risk for and protection against severe mental disorders.

NIMH is encouraging investigators to pursue innovative or novel analytical strategies to look across the human genome, and to place particular emphasis on the non-coding variants.

For several years, researchers have been finding greater instability in the genomes of people with severe mental disorders, "but these duplications and deletions encompass many genes and are very complex," Lehner said.

Researchers have been scanning for de novo mutations for a while, with the notion that people with severe mental disorders may be less likely to reproduce.

However, "for various reasons, we haven't looked across the genome at the sequence level, which would give you the best resolution" on all variation, "including common variations, rare variations, and variation in the non-coding regions," Lehner said.

"When you look at all the results from the association studies of common variants, many of those hits — the majority, actually — are in non-coding regions. So, there's definitely something going on — how the genes are turned on, turned off, and regulated in general — that happens in those non-coding regions," he told GWDN.

For these projects, the investigators are expected to consider phenotypes, disease-related covariates, and to study the significance of disease associations for common, rare, and unique sequences. The researchers also should plan to describe how structural rearrangements, insertions, deletions, and haplotypes as genomic changes will be analyzed and correlated with disease status.

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