Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Inter-annual variation in winter distribution impacts individual seabird contamination with mercury

Acknowledgments This study is part of several research programs supported by the French Agency for National Research (MAMBA project ANR-16-TERC-0004, ILETOP project ANR-16-CE34-0005), the French Arctic Initiative - CNRS (PARCS project), the Mission pour l'Interdisciplinarité - CNRS (Changements en Sibérie project), the French Polar Institute (IPEV - Pgr 388 ADACLIM) and the European Commission (Marie Curie IEF to J.F., Project 273061). This study represents a contribution to the French Polar Institute ADACLIM research program (IPEV Pgr 388). C.A is supported by a PhD fellowship from the French Ministry of higher education and research. Thanks to the CPER (Contrat de Projet Etat-Région) and the FEDER (Fonds Européen de Développement Régional) for funding the AMA and the IRMS of LIENSs laboratory. We thank the plateforme analytique of the Institut du Littoral, Environnement et Sociétés (LIENSs) and Maud Brault-Favrou for the technical support on the Hg analyses. Fieldwork on Eynhallow was conducted under permits from the British Trust for Ornithology for catching and instrumenting fulmars, and the UK Home Office for feather sampling. We thank Orkney Islands Council for access to this colony. The deployment and retrieval of GLS-loggers, and sampling of feathers and blood were conducted as part of the SEATRACK-program (www.seapop.no/en/seatrack/) in Northern Europe (Norwegian and UK colonies) made possible through close cooperation with the SEAPOP program (www.seapop.no, Norwegian Research Council grant #192141) and ARCTOX network (arctox.cnrs.fr). The work was supported by a grant (232019) from the Fram Center flagship “Climate Change in Fjord and Coast” to BM.Peer reviewedPostprin

The year-round distribution of Northeast Atlantic seabird populations : Applications for population management and marine spatial planning

Acknowledgement We thank all the fieldworkers for their hard work collecting data. Funding for this study was provided by the Norwegian Ministry for Climate and the Environment, the Norwegian Ministry of Foreign Affairs and the Norwegian Oil and Gas Association along with eight oil companies through the SEATRACK project (www.seapop.no/en/seatrack). Fieldwork in Norwegian colonies (incl. Svalbard and Jan Mayen) was supported by the SEAPOP program (www.seapop.no grant number 192141). The French Polar Institute Paul Emile Victor, funded the ORNITHO-ENDOCRINO program (IPEV program 330 to O. Chastel) on Kongsfjord kittiwakes. Russian field operations were enabled by the crew on SY Alter Ego and Open Ocean project team. A.V. Ezhov and Yu.V. Krasnov were supported by the project No 0228-2019-0004 “Ornithofauna of the northern seas: peculiarities of the nonbreeding season” with the framework of MMBI research plan and the state order for 2109-2021. The work on the Isle of May was supported by the Natural Environment Research Council (Award NE/R016429/1 as part of the UK-SCaPE programme delivering National Capability). ES Hansen was supported by VeiðikortasjóðurPeer reviewedPublisher PD