Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Pharmacogenomics of antimicrobial agents

Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use

At a crossroads:The late Eocene flora of central Myanmar owes its composition to plate collision and tropical climate

Myanmar was shaped by the India–Asia collision, fusion of the Burma Terrane (BT) with Asia, and mountain building. Throughout this process new elevational gradients and habitats were formed, which affected the regional climate, but also forged new dispersal routes into Asia and India. In spite of its importance, the vegetation history of Myanmar is poorly known, and this hinders our understanding on the origins and evolution of SE Asian biodiversity. In this study we reconstruct the late Eocene flora in central Myanmar, based on samples from a sedimentary succession in Kalewa, and extend on the Sapotaceae fossil record with additional early Eocene–early Oligocene samples. We then study the morphology, botanical affinity, source ecology and biogeography of selected sporomorphs, and assess the Gondwanan and Laurasian components. Our results show that the Eocene palynoflora is representative for evergreen forests, typical in a seasonal wet climate, with dryer vegetation away from the area of sedimentation. The abundance of Sapotaceae further suggests that this family became an important component of the SE Asian flora shortly after the India–Asia collision. We conclude that the late Eocene geographic position and Gondwanan origin of Myanmar facilitated floristic exchange between the Indian Plate, BT, mainland and SE Asia, making the BT a crossroads for plant dispersals between Gondwana and Laurasia. The shift from late Eocene seasonal evergreen to present-day moist deciduous forests was likely due to the northward drift of Myanmar, the subsequent two-stage uplift of the Indo-Burman Ranges and posterior Neogene global cooling and drying.Monsoons of Asia caused Greenhouse to Icehouse Coolin

Burma Terrane Collision and Northward Indentation in the Eastern Himalayas Recorded in the Eocene‐Miocene Chindwin Basin (Myanmar)

International audienceThe Burma Terrane (Myanmar) played an important role in the India-Asia collision and moved over 2000 km northward on the Indian Plate during the Cenozoic, before colliding with the Asian margin. However, the timing of this collision and its correlation to regional uplift phases, sedimentary provenance and basin development, remain poorly constrained. We report sedimentological, paleomagnetic and geochronological data from the late Eocene to early Miocene strata of the Chindwin Basin in the Burmese forearc, constraining the paleogeographic evolution of the Burma Terrane and the Eastern Himalayan orogen. Our results highlight two unconformities of late Eocene-middle Oligocene and latest Oligocene-early Miocene age, revealing a two stage interaction of the Burma Terrane with the Asian margin during its northward translation. The first unconformity follows rapid ~0.6 m/k.y. subsidence in the Burmese forearc, as shown by magnetostratigraphy. The transition to a fluvial depositional environment and the occurrence of reworked sediments at this first unconformity likely records the commencing collision of India and the northern extent of the Burma Terrane with the Asian margin. The second unconformity shows drastic changes in magnetic properties, mineralogy and provenance, with high-grade metamorphic grains and early Miocene apatite U-Pb and fission track ages indicating that it is coeval to a major deformation phase in Myanmar and the Eastern Himalayan orogen. It likely records the indentation of the Burma Terrane into the Eastern Himalayan collision zone, forming the modern Eastern Himalayan Syntaxis

Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy

10.1167/iovs.07-0860Investigative Ophthalmology and Visual Science4962613-261

A proto-monsoonal climate in the late Eocene of Southeast Asia: Evidence from a sedimentary record in central Myanmar

The Burma Terrane has yielded some of the earliest pieces of evidence for monsoonal rainfall in the Bay of Bengal. However, Burmese ecosystems and their potential monsoonal imprint remain poorly studied. This study focuses on the late Eocene Yaw Formation (23° N) in central Myanmar, which was located near the equator (c. 5° N) during the Eocene. We quantitatively assessed the past vegetation, climate, and depositional environments with sporomorph diagrams, bioclimatic analysis, and sequence biostratigraphy. We calculated the palynological diversity and drew inferences with rarefaction analysis by comparing with four other middle to late Eocene tropical palynofloras. Palynological results highlight a high floristic diversity for the palynoflora throughout the section formed by six pollen zones characterized by different vegetation. They indicate that lowland evergreen forests and swamps dominated in the Eocene Burmese deltaic plains while terra firma areas were occupied by seasonal evergreen, seasonally dry, and deciduous forests. This vegetation pattern is typical to what is found around the Bay of Bengal today and supports a monsoon-like climate at the time of the Yaw Formation. Bioclimatic analysis further suggests that in the late Eocene, the Yaw Formation was more seasonal, drier, and cooler compared to modern-day climate at similar near-equatorial latitude. More seasonal and drier conditions can be explained by a well-marked seasonal migration of the Intertropical Convergence Zone (ITCZ), driver of proto-monsoonal rainfall. Cooler temperatures in the late Eocene of central Myanmar may be due to the lack of adequate modern analogues for the Eocene monsoonal climate, while those found at other three Eocene Asian paleobotanical sites (India and South China) may be caused by the effect of canopy evapotranspirational cooling. Our data suggest that paleoenvironmental change including two transgressive–regressive depositional sequences is controlled by global sea level change, which may be driven by climate change and tectonics. The high diversity of the Yaw Formation palynoflora, despite well-marked seasonality, is explained by its crossroads location for plant dispersals between India and Asia

A proto-monsoonal climate in the late Eocene of Southeast Asia: Evidence from a sedimentary record in central Myanmar

The Burma Terrane has yielded some of the earliest pieces of evidence for monsoonal rainfall in the Bay of Bengal. However, Burmese ecosystems and their potential monsoonal imprint remain poorly studied. This study focuses on the late Eocene Yaw Formation (23° N) in central Myanmar, which was located near the equator (c. 5° N) during the Eocene. We quantitatively assessed the past vegetation, climate, and depositional environments with sporomorph diagrams, bioclimatic analysis, and sequence biostratigraphy. We calculated the palynological diversity and drew inferences with rarefaction analysis by comparing with four other middle to late Eocene tropical palynofloras. Palynological results highlight a high floristic diversity for the palynoflora throughout the section formed by six pollen zones characterized by different vegetation. They indicate that lowland evergreen forests and swamps dominated in the Eocene Burmese deltaic plains while terra firma areas were occupied by seasonal evergreen, seasonally dry, and deciduous forests. This vegetation pattern is typical to what is found around the Bay of Bengal today and supports a monsoon-like climate at the time of the Yaw Formation. Bioclimatic analysis further suggests that in the late Eocene, the Yaw Formation was more seasonal, drier, and cooler compared to modern-day climate at similar near-equatorial latitude. More seasonal and drier conditions can be explained by a well-marked seasonal migration of the Intertropical Convergence Zone (ITCZ), driver of proto-monsoonal rainfall. Cooler temperatures in the late Eocene of central Myanmar may be due to the lack of adequate modern analogues for the Eocene monsoonal climate, while those found at other three Eocene Asian paleobotanical sites (India and South China) may be caused by the effect of canopy evapotranspirational cooling. Our data suggest that paleoenvironmental change including two transgressive–regressive depositional sequences is controlled by global sea level change, which may be driven by climate change and tectonics. The high diversity of the Yaw Formation palynoflora, despite well-marked seasonality, is explained by its crossroads location for plant dispersals between India and Asia

Paleogene evolution of the Burmese forearc basin and implications for the history of India-Asia convergence

The geological history of the Burmese subduction margin, where India obliquely subducts below Indochina, remains poorly documented although it is key to deciphering geodynamic models for the evolution of the broader Tibetan-Himalayan orogen. Various scenarios for the evolution of the orogen have been proposed, including a collision of India with Myanmar in the Paleogene, a significant extrusion of Myanmar and Indochina from the India-Asia collision zone, or very little change in paleogeography and subduction regime since the India-Asia collision. This article examines the history of the Burmese forearc basin, with a particular focus on Eocene–Oligocene times to reconstruct the evolution of the Burmese margin during the early stages of the India-Asia collision. We report on sedimentological, geochemical, petrographical, and geochronological data from the Chindwin Basin—the northern part of the Burmese forearc—and integrate these results with previous data from other basins in central Myanmar. Our results show that the Burmese margin acted as a regular Andean-type subduction margin until the late middle Eocene, with a forearc basin that was open to the trench and fed by the denudation of the Andean volcanic arc to the east. We show that the modern tectonic configuration of central Myanmar formed 39–37 million years ago, when the Burmese margin shifted from an Andean-type margin to a hyper-oblique margin. The forearc basin was quickly partitioned into individual pull-apart basins, bounded to the west by a quickly emerged accretionary prism, and to the east by synchronously exhumed basement rocks, including coeval high-grade metamorphics. We interpret this shift as resulting from the onset of strike-slip deformation on the subduction margin leading to the formation of a paleo-sliver plate, with a paleo fault system in the accretionary prism, pull-apart basins in the forearc, and another paleo fault system in the backarc. This evolution implies that hyper-oblique convergence below the Burmese margin is at least twice older than previously thought. Our results reject any India-Asia convergence scenario involving an early Paleogene collision of India with Myanmar. In contrast, our results validate conservative geodynamic models arguing for a close-to-modern pre-collisional paleogeometry for the Indochina Peninsula, and indicate that any post-collisional rotation of Indochina, if it occurred at all, must have been achieved by the late middle Eocene