Implementing genetic education in primary care: the Gen-Equip programme

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesGenetics and genomics are increasingly relevant to primary healthcare but training is unavailable to many practitioners. Education that can be accessed by practitioners without cost or travel is essential. The Gen-Equip project was formed to provide effective education in genetics for primary healthcare in Europe and so improve patient care. Partners include patient representatives and specialists in genetics and primary care from six countries. Here, we report the progress and challenges involved in creating a European online educational program in genetics.European Unio

A sequence variant associating with educational attainment also affects childhood cognition

Only a few common variants in the sequence of the genome have been shown to impact cognitive traits. Here we demonstrate that polygenic scores of educational attainment predict specific aspects of childhood cognition, as measured with IQ. Recently, three sequence variants were shown to associate with educational attainment, a confluence phenotype of genetic and environmental factors contributing to academic success. We show that one of these variants associating with educational attainment, rs4851266-T, also associates with Verbal IQ in dyslexic children (P=4.3 x 10(-4), beta=0.16 s.d.). The effect of 0.16 s.d. corresponds to 1.4 IQ points for heterozygotes and 2.8 IQ points for homozygotes. We verified this association in independent samples consisting of adults (P=8.3 x 10(-5), beta=0.12 s.d., combined P=2.2 x 10(-7), beta=0.14 s.d.). Childhood cognition is unlikely to be affected by education attained later in life, and the variant explains a greater fraction of the variance in verbal IQ than in educational attainment (0.7% vs 0.12%,. P=1.0 x 10(-5))

A sequence variant associating with educational attainment also affects childhood cognition

Only a few common variants in the sequence of the genome have been shown to impact cognitive traits. Here we demonstrate that polygenic scores of educational attainment predict specific aspects of childhood cognition, as measured with IQ. Recently, three sequence variants were shown to associate with educational attainment, a confluence phenotype of genetic and environmental factors contributing to academic success. We show that one of these variants associating with educational attainment, rs4851266-T, also associates with Verbal IQ in dyslexic children (P=4.3 x 10(-4), beta=0.16 s.d.). The effect of 0.16 s.d. corresponds to 1.4 IQ points for heterozygotes and 2.8 IQ points for homozygotes. We verified this association in independent samples consisting of adults (P=8.3 x 10(-5), beta=0.12 s.d., combined P=2.2 x 10(-7), beta=0.14 s.d.). Childhood cognition is unlikely to be affected by education attained later in life, and the variant explains a greater fraction of the variance in verbal IQ than in educational attainment (0.7% vs 0.12%,. P=1.0 x 10(-5))

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/

Ground-Based measurements of the 2014-2015 holuhraun volcanic cloud (Iceland)

The 2014-2015 Bárðarbunga fissure eruption at Holuhraun in central Iceland was distinguished by the high emission of gases, in total 9.6 Mt SO2, with almost no tephra. This work collates all ground-based measurements of this extraordinary eruption cloud made under particularly challenging conditions: remote location, optically dense cloud with high SO2 column amounts, low UV intensity, frequent clouds and precipitation, an extensive and hot lava field, developing ramparts, and high-latitude winter conditions. Semi-continuous measurements of SO2 flux with three scanning DOAS instruments were augmented by car traverses along the ring-road and along the lava. The ratios of other gases/SO2 were measured by OP-FTIR, MultiGAS, and filter packs. Ratios of SO2/HCl = 30-110 and SO2/HF = 30-130 show a halogen-poor eruption cloud. Scientists on-site reported extremely minor tephra production during the eruption. OPC and filter packs showed low particle concentrations similar to non-eruption cloud conditions. Three weather radars detected a droplet-rich eruption cloud. Top of eruption cloud heights of 0.3-5.5 km agl were measured with ground-and aircraft-based visual observations, web camera and NicAIR II infrared images, triangulation of scanning DOAS instruments, and the location of SO2 peaks measured by DOAS traverses. Cloud height and emission rate measurements were critical for initializing gas dispersal simulations for hazard forecasting

GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures

© 2019, The Author(s). Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density

Genetic insight into sick sinus syndrome

Aims. The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results. We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10⁻²⁰), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). Conclusion. We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS

Demersal Fish Assemblages and Spatial Diversity Patterns in the Arctic-Atlantic Transition Zone in the Barents Sea

Direct and indirect effects of global warming are expected to be pronounced and fast in the Arctic, impacting terrestrial, freshwater and marine ecosystems. The Barents Sea is a high latitude shelf Sea and a boundary area between arctic and boreal faunas. These faunas are likely to respond differently to changes in climate. In addition, the Barents Sea is highly impacted by fisheries and other human activities. This strong human presence places great demands on scientific investigation and advisory capacity. In order to identify basic community structures against which future climate related or other human induced changes could be evaluated, we analyzed species composition and diversity of demersal fish in the Barents Sea. We found six main assemblages that were separated along depth and temperature gradients. There are indications that climate driven changes have already taken place, since boreal species were found in large parts of the Barents Sea shelf, including also the northern Arctic area. When modelling diversity as a function of depth and temperature, we found that two of the assemblages in the eastern Barents Sea showed lower diversity than expected from their depth and temperature. This is probably caused by low habitat complexity and the distance to the pool of boreal species in the western Barents Sea. In contrast coastal assemblages in south western Barents Sea and along Novaya Zemlya archipelago in the Eastern Barents Sea can be described as diversity “hotspots”; the South-western area had high density of species, abundance and biomass, and here some species have their northern distribution limit, whereas the Novaya Zemlya area has unique fauna of Arctic, coastal demersal fish. (see Information S1 for abstract in Russian)