Thursday, February 10th at 12pm EST/18:00 CET
Candidate gene studies have taught us little about trait genetics but a lot about the fallibility of the scientific process
Join us for a conversation with Matt Keller, Associate Professor in the Dept. of Psychology & Neuroscience at the University of Colorado, Boulder. The candidate gene (CG) approach has been used for 30 years to investigate the influence of specific polymorphisms in genes thought a-priori to be related to complex traits. Thousands of such studies have been and continue to be conducted, most reporting significant associations. In the last 15 years, a much different approach, the genome-wide association study (GWAS), has been used to investigate nearly all common genetic polymorphisms across the genome at once. Using sample sizes orders of magnitude larger than typical CG studies, GWASs have made tens of thousands of reliable discoveries, but the effect sizes are typically much smaller than those detected in CG studies, and specific CG hypotheses have failed to replicate when directly interrogated in GWAS data. What might explain these apparent contradictions? It is possible that CG studies measure traits with higher precision or that they investigate less complex “endophenotypes,” but neither explanation holds up under scrutiny. Rather, CG studies suffer from many factors—publication bias, inconsistent methodological practices, low priors, and low power—that increase the false positive rate in any field. We argue that the many positive findings using the GC approach are largely false positives and are a humbling reminder of the fallibility of the scientific process as currently practiced.
Attendees are encouraged to read Duncan and Keller 2011, “A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry” and Border et al. 2019, “No support for historical candidate gene or candidate gene-by-interaction hypotheses for major depression across multiple large samples.” Attendees may also be interested in a response to critique (Border et al. 2019) and a popular media article about this research (Yong). Sign up here for the meeting link: https://duke.zoom.us/meeting/register/tJEodOqsqD4qGtIh9AW_utDNUiz9ubSHwDw5.
Thursday, February 24th at 12pm EST/18:00 CET: Evolutionary medicine helps explain regional differences in pandemic dynamics: immunity, symbiosis, and COVID-19
Join us for a conversation with William Parker, CEO of WPLabs, Inc., and Dawit Wolday, Associate Professor of Medicine at Mekelle University College of Health Sciences. Data have been mounting for more than 50 years pointing toward the importance of “complex eukaryotic symbionts” in immune system development and function. These symbionts include protists, cestodes and nematodes, most of which have been lost to humans in high-income countries. Such loss is a direct result of the much-needed introduction of “systems hygiene” that effectively prevents pandemics of some communicable diseases. Unfortunately, available evidence indicates that the loss of complex eukaryotic symbionts in high-income countries can be defined as an evolutionary mismatch that leads to immune dysregulation and pathologic inflammation. With the immunological effects of these symbionts in mind, the speakers predicted that the presence of complex eukaryotic symbionts in areas without extensive systems hygiene would effectively decrease the clinical impact of COVID-19. This prediction was subsequently supported strongly by epidemiological evidence and eventually borne out in a study by Tobias Rinke de Wit, Dawit Wolday and colleagues in Ethiopia. Thus, evolutionary medicine proved a useful tool in understanding and anticipating regional differences in the clinical impact of COVID-19, and points toward the vital importance of understanding symbiotic relationships in the context of evolution and medicine.
Attendees are encouraged to read Parker et al. 2021, “Between a hygiene rock and a hygienic hard place: avoiding SARS-CoV-2 while needing environmental exposures for immunity” and Wolday et al. 2021, “Effect of co-infection with intestinal parasites on COVID-19 severity: a prospective observational cohort study.” Sign up here for the meeting link: https://duke.zoom.us/meeting/register/tJ0ucOmopjkuGtEnHVSe_bx-9cfLBWb2Ir5A.