Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

: Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.<br/

Fracture kinematics and holocene stress field at the krafla rift, northern iceland

In the Northern Volcanic Zone of Iceland, the geometry, kinematics and offset amount of the structures that form the active Krafla Rift were studied. This rift is composed of a central volcano and a swarm of extension fractures, normal faults and eruptive fissures, which were mapped and analysed through remote sensing and field techniques. In three areas, across the northern, central and southern part of the rift, detailed measurements were collected by extensive field surveys along the post-Late Glacial Maximum (LGM) extension fractures and normal faults, to reconstruct their strike, opening direction and dilation amount. The geometry and the distribution of all the studied structures suggest a northward propagation of the rift, and an interaction with the H\ufasav\uedk\u2013Flatey Fault. Although the opening direction at the extension fractures is mostly normal to the general N\u2013 S rift orientation (average value N99.5\ub0 E), a systematic occurrence of subordinate transcurrent com-ponents of motion is noticed. From the measured throw at each normal fault, the heave was calcu-lated, and it was summed together with the net dilation measured at the extension fractures; this has allowed us to assess the stretch ratio of the rift, obtaining a value of 1.003 in the central sector, and 1.001 and 1.002 in the northern and southern part, respectively

An analysis of the nonlinear magma-edifice coupling at Grimsvötn volcano (Iceland)

International audienceContinuous monitoring of seismicity and surface displacement of active volcanoes can reveal important features of the eruptive cycle. Here high-quality GPS and earthquake data recorded at Grimsvotn volcano by the Icelandic Meteorological Office during the 2004-2011 intereruptive period are analyzed. These showed a characteristic pattern, with an initial similar to 2 year long exponential decay followed by similar to 3 year long constant surface displacement inflation rate. We model it by using a one magma reservoir model in an elastic damaging edifice, with incompressible magma and constant pressure at the base of the magma conduit. Seismicity rate and damage were first modeled, and simple analytical expressions were derived for the magma reservoir overpressure and surface displacement as functions of time. Very good fits of the seismicity and surface displacement data were obtained by fitting only three phenomenological parameters. Characteristic time and power strain show maxima from which reference times were inferred that split the intereruptive period into five periods. After the pressurization periods, damage occurring in the third period induced weakly nonlinear variations in magma overpressure and flow, and surface displacement. During the fourth period, the damage dominated and variations became more strongly nonlinear, the reservoir overpressure decreased, and magma flow increased. This process lasted until the power strain reached its second maximum, where instability was generalized. This maximum is a physical limit, the occurrence of which shortly precedes rupture and, eventually, eruption. This analysis allows characterization of the state of the volcanic edifice during the intereruptive period and supports medium-term prediction of rupture and eruption

Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia. Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.Peer reviewe