Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Genome editing in food and feed production – implications for risk assessment. Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing. Background Gene technology has allowed for the transfer of genes between organisms and species, and thereby to design altered genotypes with novel traits, i.e. GMOs. A new paradigm started in the early 2000s with the development of genome-editing techniques. Unlike traditional genetic modification techniques resulting in insertion of foreign DNA fragments at random locations in the genome, the new genome-editing techniques additionally open for a few single nucleotide edits or short insertions/deletions at a targeted site in an organism’s genome. These new techniques can be applied to most types of organisms, including plants, animals and microorganisms of commercial interest. An important question is how the novel, genome-edited organisms should be evaluated with respect to risks to health and the environment. The European Court of Justice decided in 2018 to include genome-edited organisms in the GMO definition and hence in the regulatory system already in place. This implies that all products developed by genome-editing techniques must be risk-assessed within the existing regulatory framework for GMOs. The European and Norwegian regulatory frameworks regulate the production, import and placing on the market of food and feed containing, consisting of or produced from GMOs, as well as the release of GMOs into the environment. The assessment draws on guidance documents originally developed by EFSA for risk assessment of GMOs, which were drawn up mainly to address risks regarding insertion of transgenes. The new genome-editing techniques, however, provide a new continuum of organisms ranging from those only containing a minor genetic alteration to organisms containing insertion or deletion of larger genomic regions. Risk assessment of organisms developed by genome editing The present discourse on how new genome-editing techniques should be regulated lacks an analysis of whether risk assessment methodologies for GMOs are adequate for risk assessment of organisms developed through the use of the new genome-editing techniques. Therefore, this report describes the use of genome-editing techniques in food and feed production and discusses challenges in risk assessment with the regulatory framework. Specifically, this report poses the question as to whether the EFSA guidance documents are sufficient for evaluating risks to health and environment posed by genome-edited plants, animals and microorganisms. To address these questions, the report makes use of case examples relevant for Norway. These examples, intended for food and feed, include oilseed rape with a modified fatty acid profile, herbicide-tolerant and pest-resistant crops, sterile salmon, virus-resistant pigs and hornless cattle. The report considers all aspects of the stepwise approach as described in the EFSA guidance documents. Conclusions The inherent flexibility of the EFSA guidance makes it suitable to cover health and environmental risk assessments of a wide range of organisms with various traits and intended uses. Combined with the embedded case-by-case approach the guidance is applicable to genome-edited organisms. The evaluation of the guidance demonstrates that the parts of the health and environmental risk assessment concerned with novel traits (i.e. the phenotype of the organism) may be fully applied to all categories of genome-edited organisms. ............publishedVersio

Genome editing in food and feed production – implications for risk assessment. Scientific Opinion of the Scientific Steering Committee of the Norwegian Scientific Committee for Food and Environment

The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing. Background Gene technology has allowed for the transfer of genes between organisms and species, and thereby to design altered genotypes with novel traits, i.e. GMOs. A new paradigm started in the early 2000s with the development of genome-editing techniques. Unlike traditional genetic modification techniques resulting in insertion of foreign DNA fragments at random locations in the genome, the new genome-editing techniques additionally open for a few single nucleotide edits or short insertions/deletions at a targeted site in an organism’s genome. These new techniques can be applied to most types of organisms, including plants, animals and microorganisms of commercial interest. An important question is how the novel, genome-edited organisms should be evaluated with respect to risks to health and the environment. The European Court of Justice decided in 2018 to include genome-edited organisms in the GMO definition and hence in the regulatory system already in place. This implies that all products developed by genome-editing techniques must be risk-assessed within the existing regulatory framework for GMOs. The European and Norwegian regulatory frameworks regulate the production, import and placing on the market of food and feed containing, consisting of or produced from GMOs, as well as the release of GMOs into the environment. The assessment draws on guidance documents originally developed by EFSA for risk assessment of GMOs, which were drawn up mainly to address risks regarding insertion of transgenes. The new genome-editing techniques, however, provide a new continuum of organisms ranging from those only containing a minor genetic alteration to organisms containing insertion or deletion of larger genomic regions. Risk assessment of organisms developed by genome editing The present discourse on how new genome-editing techniques should be regulated lacks an analysis of whether risk assessment methodologies for GMOs are adequate for risk assessment of organisms developed through the use of the new genome-editing techniques. Therefore, this report describes the use of genome-editing techniques in food and feed production and discusses challenges in risk assessment with the regulatory framework. Specifically, this report poses the question as to whether the EFSA guidance documents are sufficient for evaluating risks to health and environment posed by genome-edited plants, animals and microorganisms. To address these questions, the report makes use of case examples relevant for Norway. These examples, intended for food and feed, include oilseed rape with a modified fatty acid profile, herbicide-tolerant and pest-resistant crops, sterile salmon, virus-resistant pigs and hornless cattle. The report considers all aspects of the stepwise approach as described in the EFSA guidance documents. Conclusions The inherent flexibility of the EFSA guidance makes it suitable to cover health and environmental risk assessments of a wide range of organisms with various traits and intended uses. Combined with the embedded case-by-case approach the guidance is applicable to genome-edited organisms. The evaluation of the guidance demonstrates that the parts of the health and environmental risk assessment concerned with novel traits (i.e. the phenotype of the organism) may be fully applied to all categories of genome-edited organisms. ............acceptedVersionpublishedVersio

Genome editing in food and feed production – implications for risk assessment. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

publishedVersio

Genome editing in food and feed production – implications for risk assessment

The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing.acceptedVersio

Genome editing in food and feed production – implications for risk assessment. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

Source at https://vkm.no/I denne rapporten vurderer Vitenskapskomiteen for mat og miljø (VKM) utfordringer knyttet til helse- og miljørisikovurdering av genomredigerte organismer til mat- og fôrproduksjon. VKM har gått gjennom veiledningen for risikovurdering av genmodifiserte organismer (GMO) som Den europeiske myndighet for næringsmiddeltrygghet (EFSA) har utviklet, og vurdert om veiledningen også kan brukes til å vurdere risiko ved organismer som er utviklet ved genomredigering. VKM har selv tatt initiativ til denne rapporten.The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing

Genome editing in food and feed production – implications for risk assessment

The Norwegian Scientific Committee for Food and Environment (VKM) initiated this work to examine the extent to which organisms developed by genome-editing technologies pose new challenges in terms of risk assessment. This report considers whether the risk assessment guidance on genetically modified organisms, developed by the European Food Safety Authority (EFSA), can be applied to evaluate potential risks of organisms developed by genome editing.acceptedVersio

Genome editing in food and feed production – implications for risk assessment. Opinion of the Steering Committee of the Norwegian Scientific Committee for Food and Environment

acceptedVersio

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures