Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Review of \u3ci\u3eThe Cherokees and Their Chiefs: In the Wake of Empire\u3c/i\u3e By Stanley W. Hoig

A popular history of the Cherokees, Hoig\u27s book recounts, through vivid prose and detailed research from Euro-American records and scholarly sources, the diverse and troubled relationships between the Cherokee people and varied agents of colonialist expansion. Those who are largely unfamiliar with the voluminous number of academic texts about the history of British/US/Cherokee interaction will find the volume quite compelling. Those looking for more contemporary research, however, or for a strong Cherokee presence among the sources chosen will find The Cherokees and Their Chiefs something of a disappointment. Hoig\u27s greatest strength is as a dynamic storyteller. Writing with clarity and passion about the powerful personalities and events involved in Cherokee resistance to displacement, removal, and detribalization, he brings t~ life such figures as Attakullakulla, Oconostota, and Dragging Canoe of the 1700s, and John Ross, Stand Watie, and the various political and social rivals who battled for primacy through the nineteenth century and its traumas of Removal, the US Civil War, and allotment. Hoig is unflinching in his acknowledgment that [s]eldom were [the Cherokees] defeated in their contests with the [US] government on the merits of their case but usually by the unwillingness of government officials to adhere to their own ethics and written laws ; he exposes frequently the shameful actions of the US and its citizens in their interactions with the Cherokee people, Unfortunately, as a scholarly text this book is lacking. It fails to draw on the most recent scholarship in the field, except in passing, and generally ignores cultural stories and oral histories of Cherokees themselves. The terminology employed is often that of pulp Westerns, complete with shamans and Indians howling and letting out their war whoop while engaging in massacre and bloody assaults on their (white) enemies. The sympathetic orientation of the stories is offset by the frequent animalistic terminology. (Yet I was more than a little amused to find that Andrew Jackson, too, howled in fury at one point,fMoreover, there is far too much of the Vanishing Indian stereotype, with references to the futility of Cherokee resistance to white intrusion, the possible demise of their tribal being, and the apparently ever-present precarious path that separates advancement from extinction. With little discussion of contemporary Cherokee culture and history, or the rich vitality and powerful endurance of the Cherokee people, such stereotypes are given an unfortunate emphasis in the text. Perhaps the greatest drawback of The Cherokees and Their Chiefs for the scholar is one of context: do we really need another generalized history of the Cherokee chiefs and their interaction with the US government? Probably not. Focusing on only the men (With scanty mention of Nancy Ward/Nanyehi and Wilma Mankiller) who stood as political leaders provides, at best, a limited perspective, especially considering the strong traditional role of women in Cherokee politics. The leading Cherokee scholarship today proVides detailed and nuanced analyses of the largely ignored or misunderstood aspects of Cherokee life: gender roles and divisions among Cherokees past and present; the diversity of responses to intermarriage, acculturation, and assimilation, and their uses in the formation of contemporary Cherokee identities; Christianity and its relationship to traditional spiritual practices; and the endurance of traditional stories, ethicS, and beliefs among today\u27s Cherokee people. Yet the flaws are largely forgivable. The book is more outdated in perspective than intentionally dismissive of more substantive analysis or current historiography. As far as it goes, The Cherokees and Their Chiefs provides a good start for anyone interested in many of the larger political and social forces dominating the lives of Cherokees in the eighteenth and nineteenth centuries

Our fire survives the storm: Removal and defiance in the Cherokee literary tradition

This study attends to the responses of Cherokees to the symbol, threat, and reality of Indian Removal, through a detailed study of the Cherokee literary tradition, including oral narratives, treaties, personal correspondence, newspaper articles, novels, poems, short stories, personal narratives, and social sciences monographs. Central to this study are Cherokee voices, scholarship, and cultural and historical perspectives, read through a methodology of the culturally-specific “Beloved Path” and “Chickamaugan consciousness,” which are drawn from Cherokee worldviews and intellectual traditions. The project begins by laying the foundation of the Beloved Path and Chickamaugan consciousness, and examining how these two philosophical understandings of traditional Cherokee society are evident in early oral narratives of pre-Trail of Tears removals, as well as in the lives of the eighteenth-century political leaders Nanyehi (Nancy Ward) and her cousin, Dragging Canoe. Arguing that these traditional approaches to Removal have endured through European and U.S. colonization, the author expands the theoretical framework into the history of the Cherokee Trail of Tears and Cherokee responses to the event. The nineteenth-century writings of Chief John Ross engage with the text of the Treaty of New Echota and writings of Elias Boudinot and John Ridge through contrasting Beloved Path and Chickamaugan consciousness expressions. Similarly, the author argues that these culturally-specific perspectives inform the Trail-centered work of contemporary writers Robert Conley, Diane Glancy, and Thomas King. The last section of this study examines the late nineteenth- and early twentieth-century expressions of the Beloved Path and Chickamaugan consciousness paradigms, as expressed in the writings of Western Cherokees Will Rogers, Lynn Riggs, and Emmet Starr, during the era of allotment and Oklahoma statehood. Interwoven into this analysis is the concept of Native intellectual sovereignty, which privileges Native intellectual traditions and practices and places them as the interpretive center of this reading. Applying the methodology of the Chickamauga consciousness to lived contemporary experience, the project also includes an examination of the author\u27s family histories of removal in a broader Cherokee context

Introduction : Indigenous conversations about biography

9 page(s