Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics.
View Article and Find Full Text PDFJ Am Acad Child Adolesc Psychiatry
July 2014
The XXI World Congress of Psychiatric Genetics (WCPG), sponsored by the International Society of Psychiatric Genetics (ISPG), took place in Boston, Massachusetts, on 17-21 October 2013. Approximately 900 participants gathered to discuss the latest findings in this rapidly advancing field. The following report was written by student travel awardees.
View Article and Find Full Text PDFThe rapid development of next-generation sequencing (NGS) technology has led to renewed interest in the potential contribution of rarer forms of genetic variation to complex non-mendelian phenotypes such as psychiatric illnesses. Although challenging, family-based studies offer some advantages, especially in communities with large families and a limited number of founders. Here we revisit family-based studies of mental illnesses in traditional Amish and Mennonite communities--known collectively as the Plain people.
View Article and Find Full Text PDFResearch suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry.
View Article and Find Full Text PDF