Study the forest, not only the trees: Environmental exposures, not genomes, generate most health disparities.

As sequencing and analysis techniques provide increasingly detailed data at a plummeting cost, it is increasingly popular to seek the answers to medical and public health challenges in the DNA sequences of affected populations. This is methodologically attractive in its simplicity, but a genomics-only approach ignores environmentally mediated health disparities, which are well-documented at multiple national and global scales. While genetic differences exist among populations, it is unlikely that these differences overcome social and environmental factors in driving the gap in health outcomes between privileged and oppressed communities. We advocate for following the lead of communities in addressing their self-identified interests, rather than treating widespread suffering as a convenient natural experiment.

Examining Cultural Structures and Functions in Biology.

Scientific culture and structure organize biological sciences in many ways. We make choices concerning the systems and questions we study. Our research then amplifies these choices into factors that influence the directions of future research by shaping our hypotheses, data analyses, interpretation, publication venues, and dissemination via other methods. But our choices are shaped by more than objective curiosity-we are influenced by cultural paradigms reinforced by societal upbringing and scientific indoctrination during training. This extends to the systems and data that we consider to be ethically obtainable or available for study, and who is considered qualified to do research, ask questions, and communicate about research. It is also influenced by the profitability of concepts like open-access-a system designed to improve equity, but which enacts gatekeeping in unintended but foreseeable ways. Creating truly integrative biology programs will require more than intentionally developing departments or institutes that allow overlapping expertise in two or more subfields of biology. Interdisciplinary work requires the expertise of large and diverse teams of scientists working together-this is impossible without an authentic commitment to addressing, not denying, racism when practiced by individuals, institutions, and cultural aspects of academic science. We have identified starting points for remedying how our field has discouraged and caused harm, but we acknowledge there is a long path forward. This path must be paved with field-wide solutions and institutional buy-in: our solutions must match the scale of the problem. Together, we can integrate-not reintegrate-the nuances of biology into our field.

DNA methylation and adiposity phenotypes: an epigenome-wide association study among adults in the Strong Heart Study.

BACKGROUND: Elevated adiposity is often posited by medical and public health researchers to be a risk factor associated with cardiovascular disease, diabetes, and other diseases. These health challenges are now thought to be reflected in epigenetic modifications to DNA molecules, such as DNA methylation, which can alter gene expression. METHODS: Here we report the results of three Epigenome Wide Association Studies (EWAS) in which we assessed the differential methylation of DNA (obtained from peripheral blood) associated with three adiposity phenotypes (BMI, waist circumference, and impedance-measured percent body fat) among American Indian adult participants in the Strong Heart Study. RESULTS: We found differential methylation at 8264 CpG sites associated with at least one of our three response variables. Of the three adiposity proxies we measured, waist circumference had the highest number of associated differentially methylated CpGs, while percent body fat was associated with the lowest. Because both waist circumference and percent body fat relate to physiology, we focused interpretations on these variables. We found a low degree of overlap between these two variables in our gene ontology enrichment and Differentially Methylated Region analyses, supporting that waist circumference and percent body fat measurements represent biologically distinct concepts. CONCLUSIONS: We interpret these general findings to indicate that highly significant regions of the genome (DMR) and synthesis pathways (GO) in waist circumference analyses are more likely to be associated with the presence of visceral/abdominal fat than more general measures of adiposity. Our findings confirmed numerous CpG sites previously found to be differentially methylated in association with adiposity phenotypes, while we also found new differentially methylated CpG sites and regions not previously identified.

Social density, but not sex ratio, drives ecdysteroid hormone provisioning to eggs by female house crickets (Acheta domesticus).

Social environment profoundly influences the fitness of animals, affecting their probability of survival to adulthood, longevity, and reproductive output. The social conditions experienced by parents at the time of reproduction can predict the social environments that offspring will face. Despite clear challenges in predicting future environmental conditions, adaptive maternal effects provide a mechanism of passing environmental information from parent to offspring and are now considered pervasive in natural systems. Maternal effects have been widely studied in vertebrates, especially in the context of social environment, and are often mediated by steroid hormone (SH) deposition to eggs. In insects, although many species dramatically alter phenotype and life-history traits in response to social density, the mechanisms of these alterations, and the role of hormone deposition by insect mothers into their eggs, remains unknown. In the experiments described here, we assess the effects of social environment on maternal hormone deposition to eggs in house crickets (Acheta domesticus). Specifically, we tested the hypotheses that variable deposition of ecdysteroid hormones (ESH) to eggs is affected by both maternal (a) social density and (b) social composition. We found that while maternal hormone deposition to eggs does not respond to social composition (sex ratio), it does reflect social density; females provision their eggs with higher ESH doses under low-density conditions. This finding is consistent with the interpretation that variable ESH provisioning is an adaptive maternal response to social environment and congruent with similar patterns of variable maternal provisioning across the tree of life. Moreover, our results confirm that maternal hormone provisioning may mediate delayed density dependence by introducing a time lag in the response of offspring phenotype to population size.

Environmental causes and transgenerational consequences of ecdysteroid hormone provisioning in Acheta domesticus.

An animal's phenotype may be shaped by its genes, but also reflects its own environment and often that of its parents. Nongenetic parental effects are often mediated by steroid hormones, and operate between parents and offspring through mechanisms that are well described in vertebrate and model systems. However, less is understood about the strength and frequency of hormone mediated nongenetic parental effects across more than one generation of descendants, and in nonmodel systems. Here we show that the concentration of active ecdysteroid hormones provided by a female house cricket (Acheta domesticus) affects the growth rate of her offspring. We also reveal that variation in the active ecdysteroid hormones provided by a female house cricket to her eggs derives primarily from the quality of nutrition available to her maternal grandmother, regardless of genetic background. This finding is in stark contrast to most previous work that documents a decline in the strength of environmentally based parental effects with each passing generation. Strong grandparental effects may be adaptive under predictable, cyclical changes in the environment. Our results also suggest that hormone-mediated grand-maternal effects represent an important potential mechanism by which organisms can respond to environmental variability, and that further study of hormone-mediated carryover effects in this context could be profitable.