Pedigree Sequencing Working Group
Work with us!
If you have questions regarding the Pedigree workgroup or projects that are currently being conducted, please contact the workgroup chair.
About Us
The Pedigree Working Group, based at Trinity College Dublin (TCD), has been part of the Psychiatric Genomics Consortium since 2018. Since that time, we have developed robust pipelines for the analysis of whole genome sequence pedigree data. Our rationale is to identify large, multiply affected pedigrees with one, or more, major psychiatric disorders to investigate for rare risk mutations. To date we have worked with 10 research groups across three continents. Our aim is to expand our programme to work with other interested groups in this area, and to increase the diversity and range of both pedigrees and disorders that we work with.
Our Motivation
Identifying rare, risk mutations of moderate, or large effect, may be particularly informative in understanding the biology of mental disorders. Traditional pedigree studies investigated single disorders, but we are increasingly realizing that this class of variation is pleiotropic, particularly overlapping neurodevelopmental disorders. More damaging mutations are likely to be selected against in the human population, and as such, may be easier to identify in family clusters than in large case-control samples.
Who we are
Our current working group includes Dr Aiden Corvin, Dr Eleisa Heron, Dr Niamh Ryan, and Dr Cathal Ormond. We are interested in increasing our membership and holding regular workgroup meetings to progress this work.
Major accomplishments
We have developed methods to facilitate conversion of data between genome builds (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425424/pdf/bbab069.pdf), a pipeline for CNV analysis in pedigree data (currently under review) and are developing a Bayesian analytical approach to pedigree analysis.
With Carol Mathews and colleagues, we have published whole genome sequencing analysis of an 11-generation Costa Rican pedigree densely affected with Tourette Syndrome (TS). In this work we identified three ultra-rare deleterious mutations implicating neurodevelopmental genes in TS biology (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763103/pdf/41380_2022_Article_1771.pdf).
In an investigation of US schizophrenia pedigrees with Dr. Bill Byerley we have identified co-segregation with a gene involved in calcium homeostasis (ATP2B2) and evidence of enrichment of missense variants at this gene in the large SCHEMA schizophrenia case-control cohort https://www.sciencedirect.com/science/article/pii/S2667174323000101?via=ihub)
Get Involved!
Currently, we are looking for new collaborators with pedigree data in order to increase discovery and to start to look at cross-pedigree and cross diagnostic analysis. We are also looking to increase participants of diverse ancestry. If you would like to be part of this work please contact Dr. Aiden Corvin.
Funders
