FROM DSM TO DNA: CROSS-DISORDER GENETICS AND THE IMPLICATIONS OF PLEIOTROPY

Abstract

As large-scale genomic research has begun to sketch the genetic architecture of mental illness, there is increasing evidence that genetic influences transcend the clinically-defined boundaries of psychiatric disorders. Collaborative efforts, including the Psychiatric Genomics Consortium’s Cross-Disorder Group and the Brainstorm initiative are providing new insights into the genetic relationships among these disorders while challenging assumptions about the structure of psychopathology. A growing catalogue of common and rare genetic loci appear to have pleiotropic effects on multiple neuropsychiatric phenotypes. Polygenic risk score analyses and common variant genetic correlation studies support earlier findings from family and twin studies that a range of disorders have shared genetic substrates. At the same time, genomic studies suggest that there may be no sharp boundaries between disorder and normal variation in psychopathology-related traits. This presentation will review emerging evidence and key questions about cross-disorder genetic effects and the implications of pleiotropy for psychiatric nosology.