Genome-wide association studies have underpinned our understanding of the genetics of psychiatric illness, among many other complex traits, confirming the heritability of schizophrenia, its polygenicity and its genetic overlap with bipolar disorder and major depressive disorder. Amid the ever-expanding meta-analyses that rightfully now include multiple ethnicities is there a place for studying large multiplex families?

I will present the analyses of a single such family over more than 50 years highlighting the value of such detailed studies to our understanding of psychiatric illness and what questions remain. I will talk about some of the mistakes we made, some to our benefit and others not, as well as how in Edinburgh this research expanded beyond statistical genetics to involve multidisciplinary teams worldwide. Finally, I will present preliminary results from the Pedigree-Based Whole Genome Sequencing of Affective and Psychotic Disorders consortium and discuss the use of pedigree analyses in the era of whole genome sequencing.

Supported by the Trinity College Dublin, Faculty of Health Sciences Visiting Professor Fund 2026