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The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
This fourth paper in the NSW Vegetation Classification and Assessment series covers the Brigalow Belt South-/1(BBS) and Nandewar (NAN) Bioregions and the western half of the New England Bioregion (NET), an area of 9.3 million hectares being 11.6% of NSW. It completes the NSWVCA coverage for the Border Rivers-Gwydir and Namoi CMA areas and records plant communities in the Central West and Hunter–Central Rivers CMA areas. In total, 585 plant communities are now classified in the NSWVCA covering 11.5 of the 18 Bioregions in NSW (78% of the State). Of these 226 communities are in the NSW Western Plains and 416 are in the NSW Western Slopes. 315 plant communities are classified in the BBS, NAN and west-NET Bioregions including 267 new descriptions since Version 2 was published in 2008. Descriptions of the 315 communities are provided in a 919 page report on the DVD accompanying this paper along with updated reports on other inland NSW bioregions and nine Catchment Management Authority areas fully or partly classified in the NSWVCA to date. A read-only version of Version 3 of the NSWVCA database is on the DVD for use on personal computers. A feature of the BBS and NAN Bioregions is the array of ironbark and bloodwood Eucalyptusdominated shrubby woodlands on sandstone and acid volcanic substrates extending from Dubbo to Queensland. This includes iconic natural areas such as Warrumbungle and Mount Kaputar National Parks and the 500,000 ha Pilliga Scrub forests. Large expanses of basalt-derived soils support grassy box woodland and native grasslands including those on the Liverpool Plains; near Moree; and around Inverell, most of which are cleared and threatened. Wetlands occur on sodic soils near Yetman and in large clay gilgais in the Pilliga region. Sedgelands are rare but occupy impeded creeks. Aeolian lunettes occur at Narran Lake and near Gilgandra. Areas of deep sand contain Allocasuarina, eucalypt mallee and Melaleuca uncinata heath. Tall grassy or ferny open forests occur on mountain ranges above 1000m elevation in the New England Bioregion and on the Liverpool Range while grassy box woodlands occupy lower elevations with lower rainfall and higher temperatures. The vegetation classification and assessment is based on over 100 published and unpublished vegetation surveys and map unit descriptions, expert advice, extra plot sampling and data analysis and over 25 000 km of road traverse with field checking at 805 sites. Key sources of data included floristic analyses produced in western regional forest assessments in the BBS and NAN Bioregions, floristic analyses in over 60 surveys of conservation reserves and analysis of plot data in the western NET Bioregion and covering parts of the Namoi and Border Rivers- Gwydir CMA areas. Approximately 60% of the woody native vegetation in the study area has been cleared resulting in large areas of “derived” native grasslands. As of June 2010, 7% of the area was in 136 protected areas and 127 of the 315 plant communities were assessed to be adequately protected in reserves. Using the NSWVCA database threat criteria, 15 plant communities were assessed as being Critically Endangered, 59 Endangered, 60 Vulnerable, 99 Near Threatened and 82 Least Concern. 61 of these communities are assessed as part of NSW or Commonwealth-listed Threatened Ecological Communities. Current threats include expanding dryland and irrigated cropping on alluvial plains, floodplains and gently undulating topography at lower elevations; over-grazing of steep hills; altered water tables and flooding regimes; localized mining; and the spread of exotic species, notably Coolatai Grass (Hyparrhenia hirta).
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.