Thomas S. Wingo, Ph.D., MD

Department of Neurology

Phone: 404-727-4905

Email: thomas.wingo@emory.edu

Biography

The overarching goal of my research is to identify the genetic causes of neurodegenerative diseases, particularly Alzhiemer's disease (AD), Frontotemporal dementia (FTD), and Amyotrophic Lateral Sclerosis (ALS). To that end, I am a board-certified Neurologist with further subspecialty training in neurocognitive illnesses with an emphasis on degenerative diseases associated with older age. My post-doctoral work included: (1) training in population genetics and modern genetic techniques and (2) developing programming and bioinformatics skills.

Since becoming an Assistant Professor at Emory University, I developed a keen interest in understanding the underlying genetic architecture of AD. In our first study, we used family history data previously collected on approximately 5,800 individuals with AD by 29 national Alzheimer's Disease Research Centers to perform the largest heritability of AD to date. Unsurprisingly, we found that when AD occurs on or after 65 years it is entirely consistent with being a polygenic disease; however, our results for individuals with early-onset AD (AD occurring before or at 60 years; EOAD) suggest that it is not a substantially polygenic disease. Indeed, it is well-known that only ~10% of individuals with EOAD carry autosomal dominant mutations. Thus, the question is what causes the remaining 90% of EOAD. The most straightforward explanation of the data is that there are autosomal recessive causes of EOAD, and addressing this hypothesis is currently the focus of an R01 grant application.

To understand the role of common versus rare variants in AD, I have requested and am analyzing genome-wide genotyping on ~5,000 individuals with AD collected by the AD Genetic Consortium. This secondary analysis of that data, addresses what proportion of the variance of AD is explained by common markers and the relative contributions of known genetic risk factors to the disease.

To identify new Mendelian causes of AD or rare alleles with high-effect sizes I work with collaborators at the Emory University Alzheimer's Disease Research Center who have previously collected families with AD, both early-onset and late-onset, that appear to have dominant transmission of disease. We are using a combination of whole-exome sequencing with traditional linkage analysis to identify causal alleles in these families and test those using functional assays and resequencing candidate genes in AD cases and healthy controls over 65 years.

Finally, to understand the genetic basis of ALS and FTD, I have performed a heritability study of ALS with my collaborator, Jonathan Glass, M.D., and found that ALS has moderate heritability. Yet, it appears that a large proportion of the disease is due to monogenic causes than seen in AD. I am also collaborating with Peng Jin, Ph.D. to examine why the recently identified GGGGCC repeat expansion causes neuronal cell death using both Drosophila and mammalian model systems.

Publications