Christian Abnet

Ph.D., M.P.H.

NCI/DCEG

Senior Investigator

PLCO (Learn more about this study)

2018-1016

Dec 21, 2018

Genetic and environmental determinants of the oral microbiota

The oral microbiome appears to play key roles in human health and metabolism. Currently, we have a limited understanding of the relative contribution of host genetics, environmental factors, and lifestyle to the composition of the oral microbiome and its stability of over time. We propose to use oral wash specimens collected in PLCO at two time-points to characterize the oral microbiota of subjects in PLCO, the stability of the oral microbiota over time, and the genetic and environmental data on individual subjects to explore this question. We would select 6000 subjects from the control arm that provided buccal cell samples in 2000-2003 and again in 2017-2018. We propose to use DNA extracted from these specimens to characterize the oral microbiota at each time point. We will use DNA sequencing to characterize the overall community diversity and the relative abundance of specific taxa. These data would then be combined with the data for each individual from the Infinium Global Screening Array (GSA) to characterize common genetic variation in the host and the environmental and lifestyle exposure data from the baseline and follow-up questionnaires. We would not select based on health outcomes (i.e. there is no required ‘case’ group). We would preferentially select pairs of subjects that were known to have lived at the same address so that we can assess the relative contribution of co-habitation to the oral microbiota composition. We would also use the GSA data to preferentially select siblings or other genetically-related subjects. We would also like to assess the genomic background of individuals prior to selection. Given the potential challenges of examining people with substantially different genomes with regard to continent of origin, we think it would be prudent to pre-select subjects that can compared in the downstream genomic analyses. Therefore, using the GSA chip data we would select subjects with sufficiently similar genomic backgrounds using structure plots. This may require us to limit our project to people of European descent, but if there are sufficient subjects from other subgroups, we would be happy to include them in the study as well. With the complete data set we can establish the stability of the oral microbiota over the span of ~15 years, identify host genomic regions that help control the composition of the oral microbiota in cross-section and over time, and partition variation in the composition between host genetics, individual exposures (such as diet, tobacco, and alcohol use), and the effect of co-habitation.