Research Seminar: Variant Discovery and Clinical Interpretation

This month the research seminar will feature talks from members of the Variant Discovery and Clinical Interpretation Community. This month's talks are listed below:

Beyond monogenic familial hypercholesterolaemia: insights from the 100,000 Genomes Project

• The speaker will present a whole-genome sequencing study of clinically diagnosed familial hypercholesterolaemia in the 100,000 Genomes Project, highlighting the contributions of rare variants, polygenic predisposition, and variation in the LPA gene.
• The talk will cover rare-variant analysis in established familial hypercholesterolaemia genes, a genome-wide association study of individuals without an identified FH-causing variant, and polygenic risk scores for LDL cholesterol and lipoprotein(a).
• Attendees will gain an understanding of the diverse genetic factors underlying the familial hypercholesterolaemia phenotype and why considering polygenic contributions and measuring lipoprotein(a) alongside LDL cholesterol are important for more precise diagnosis.

-Martin Bird, Postdoctoral Research Associate in Statistical Genetics, William Harvey Research Institute, Queen Mary University of London

From gene discovery to genetic diagnosis through large-scale analysis of de novo variation

• The speaker will present ASCEND, a summary-statistics framework for jointly analysing de novo variation across rare disease trio cohorts and ASCEND-Diag, an approach for quantifying the diagnostic evidence provided by individual variants.
• The talk will discuss meta-analysis of 74,990 trios across five groups of congenital conditions, the discovery and validation of new gene–disease associations and phenotypic expansions and the estimation of variant-level diagnostic causal probabilities.
• Attendees will gain an understanding of how large-scale aggregation of trio data can connect statistical gene discovery with interpretable, quantitative evidence for individual genetic diagnoses.

-Mikhail A. Moldovan, Postdoctoral Research Fellow, Department of Biomedical Informatics, Harvard Medical School / Broad Institute of MIT and Harvard

About the speakers:

Martin Bird, Postdoctoral Research Associate in Statistical Genetics, William Harvey Research Institute, Queen Mary University of London

Martin Bird is a statistical geneticist at Queen Mary University of London, where he investigates the genetic basis of cardiovascular disease using large-scale genomic and clinical data. His interests include inherited lipid disorders and cardiac arrhythmias, with a focus on understanding disease mechanisms and improving molecular diagnosis. His work combines the study of rare genetic variants with genome-wide association analyses, polygenic risk assessment, and functional approaches.

Mikhail A. Moldovan, Postdoctoral Research Fellow, Department of Biomedical Informatics, Harvard Medical School / Broad Institute of MIT and Harvard

Mikhail Moldovan is a postdoctoral researcher in Shamil Sunyaev’s group at Harvard Medical School and the Broad Institute. His research focuses on developing statistical and computational methods for the analysis of genetic variation.

About the research seminars:

The Genomics England Research Seminar series is a season of events held to demonstrate the best research from Genomics England and our partners. They started in October 2018, and are monthly, free-to-attend talks presented by Research Network members on the latest research being performed using data from the National Genomic Research Library.

The seminars will be held on the last Tuesday of each month at 2 to 3pm. These will be online sessions open to everyone and free to attend, we hope to have representation from across the Research Network and 100,000 Genomes Project participants as well as anyone else who would be interested in joining.

For updates on the seminars including announcements and speakers please follow the Genomics England twitter page. You can watch all previous Research Seminars on the Genomics England YouTube channel.

If you would like to present your research from the Genomics England Research Environment at one of these events please get in touch with the Research Management team at [email protected] and if you intend to publish on this research please include this so that we can publicise your paper on our Publications page.