1,000 ancient genomes uncover 10,000 years of natural selection in Europe (preprint)

Ancient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.

COVID-19 outcomes of patients with gynecologic cancer in New York City: an updated analysis

Despite a growing body of literature, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes in New York City (NYC) from the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). We sought to determine the hospitalization and mortality rates and their associated factors, specifically recent chemotherapy and immunotherapy use. Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 New York City (NYC) area hospital systems. Multivariable logistic regression was utilized to analyze COVID-19 related hospitalization and mortality. Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range, 53.0-73.0 years). A total of 106 of the 193 patients (54.9%) required hospitalization;among the hospitalized patients 13 (12.3%) required invasive mechanical ventilation and 39 (36.8%) required ICU admission. No patients requiring mechanical ventilation survived. A total of 34 of 193 (17.6%) patients died of COVID-19 complications. On multivariable analysis, hospitalization was associated with an age greater than or equal to 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status greater than or equal to 2 (OR 3.67, CI 1.25, 13.55) and greater than or equal to 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 on multivariable analysis. A total of 13 of 34 (38.23%) patients who died of COVID-19 complications received cytotoxic chemotherapy, while 4 of 34 (11.76%) patients received immunotherapy. However, recent cytotoxic chemotherapy use was not predictive of COVID-19 hospitalization or mortality on multivariable analysis. [Display omitted] The case fatality rate among gynecologic oncology patients with COVID-19 infection is 17.6%. Cancer-directed therapy, including immunotherapy use, is not associated with an increased risk of mortality related to COVID-19 infection in this larger cohort. [ABSTRACT FROM AUTHOR] Copyright of Gynecologic Oncology is the property of Academic Press Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)