91社区's Seminar Series in Quantitative Life Sciences and Medicine
Sponsored by CAMBAM, QLS, MiCM and the Ludmer Centre
罢颈迟濒别:听Mapping the structure of genetic risk for common disease in the UK Biobank
厂辫别补办别谤:听Gil McVean (Oxford University)
奥丑别苍:听Tuesday, February 12, 2019, 12-1pm聽
奥丑别谤别:听Montreal Neurological Institute, DeGrandpre Communications Centre
Abstract: Genetic risk factors frequently affect multiple common human diseases, providing insight into shared pathophysiological pathways and opportunities for therapeutic development. However, systematic identification of genetic profiles of disease risk is limited by the availability of both comprehensive clinical data on population-scale cohorts and the lack of suitable statistical methodology that can handle the scale of and differential power inherent in multi-phenotype data. We have developed a disease-agnostic approach to cluster genetic risk profiles for 3,025 genome-wide independent loci across 19,155 ICD-10 diagnostic codes from 320,644 participants in the UK Biobank, representing a large and heterogeneous population. We identify several hundred distinct disease association profiles and use multiple approaches to link clusters to underlying biological pathways. We show how clusters can decompose the variance and covariance in risk for disease, thereby identifying underlying biological processes and their impact. We demonstrate the use of clusters in defining disease relationships and informing therapeutic strategies
