Research

Our research program encompasses a synthesis of methodological and applied genetic epidemiology, with the overall aim of deciphering the mechanisms underlying complex diseases and traits. Our methods work is focused on the design and statistical analysis of next-generation sequencing and genetic association studies. We are applying these methods to studies of cancer (e.g., of the prostate), birth defects, and pharmacogenomics.

Methods
We have developed extensive methods and software for studying rare genetic variants, pathways, interactions, and genome-wide association studies. For analyzing rare variants, we have recently developed novel Bayesian (Cardin, Mefford & Witte, 2012) and ‘Step-up’ empirical methods (Hoffmann, Marini & Witte, 2010). With regard to GWAS, we have determined the remaining heritability across all major traits, and the optimal approach for assessing this (Lindquist, Jorgenson, Hoffmann & Witte, 2013).

Applications
We are presently undertaking exome- and genome-wide studies of the genomic basis of prostate cancer, with a particular focus on disease aggressiveness among understudied populations. This includes a recent publication on the high-penetrance HOXB13 prostate cancer mutation (Witte et al., 2013).  We are extending this work to assess the pleiotropy (i.e., shared genetic basis) across multiple different cancers Sakoda, Jorgenson & Witte,  2013).

Witte Lab research has been generously supported by the:
•    National Institutes of Health / National Cancer Institute
•    Department of Defense
•    General Motors Foundation
•    Urologic Research Foundation
•    UCSF Department of Urology, Cancer Center, and the Institute for Human Genetics