Integration of Monogenic and Common Variants in Human Disease - CGSI 2022

Explore the integration of monogenic and common variants in human disease through this 39-minute conference talk by Val Arboleda from UCLA at the Computational Genomics Summer Institute (CGSI) 2022. Delve into the challenges of phenotyping rare diseases and the expansion of genotypic and phenotypic spectra. Examine the role of pathologists in disease classification and the complexities of sequencing. Investigate congenital heart defects and the limitations of ICD codes for phenotyping. Learn about the relationship between polygenic risk scores and odds of CHD classification. Gain insights from related research papers on phenotype-specific enrichment of Mendelian disorder genes, polygenic risk scores in congenital heart disease, and the contribution of deleterious variants to complex disease risk.

Intro
What is a Pathologist?
Sequencing is Easy
Phenotyping of rare disease spectrum of disease is challenging
Expansion of the genotypic spectrum and phenotypic spectrum
Other explanations for variable expressivity/expansion of phenotypes?
Congenital Heart Defects
ICD codes are not good phenotypes at baseline
Top decile of case control Heart Valve PRS (all SNVs) have decreased odds for a CHD classification