NAMHC Concept Clearance •
Thomas Lehner, Ph.D., MPH
Genomics Research Branch
Division of Neuroscience and Basic Behavioral Science
This initiative will support applications that propose to deposit data (genotypes and phenotypes) into an NIH Repository to augment existing resources and to analyze combined Genome Wide Association Studies (GWAS) of mental disorders of interest to the NIMH.
In the short history of the Human Genome Project, 2007 became the year when evolutionary developments in single nucleotide polymorphism (SNP) genotyping technologies made the large-scale analysis of whole genome data and their association with complex human diseases possible. This is an exciting time for the genetics of mental disorders and several large GWAS studies involving thousands of cases and controls have been conducted and published or will be published in the near future. However, the analyses of these data and data from studies in different disease areas have shown that determining the contribution of common alleles to the genetics of mental disorders requires studies with sample sizes in the tens of thousands, with subjects whose phenotypes have been carefully ascertained. Furthermore, it is likely that the common risk alleles underlying mental disorders are of modest effect size and prone to estimation errors and confounding; thus, they are highly model dependent. Combining data sets across various studies will improve power and provide the opportunity to test the association between genetic variants and sub-phenotypes for specific mental disorders. Combining data sets will also render estimates of the effect size for a single allele or a set of joint interacting alleles more precise.
This initiative will support secondary statistical analysis on existing whole genome association data sets for genetic studies of five major mental disorders, including attention-deficit hyperactivity disorder, bipolar disorder, autism spectrum disorders, major depressive disorder and schizophrenia. The applicants will be required to participate in the recently formed Psychiatric Metanalysis Consortium (PMC) and to perform innovative analyses on combined data sets across different genotyping platforms and phenotypes, using existing or newly developed statistical methods.