Publication: A compendium of uniformly processed human gene expression and splicing quantitative trait loci

Citation: Kerimov N, Hayhurst JD, Peikova K, et al. A compendium of uniformly processed human gene expression and splicing quantitative trait loci. Nat Genet. 2021;53(9):1290-1299. doi:10.1038/s41588-021-00924-w

Funding: The RNA-seq quantification and QTL analyses were performed at the High Performance Computing Center, University of Tartu. We thank E. Pihlapuu from the Grant Office of the University of Tartu, and H. Foster and P. Litterick from Open Targets for assistance in setting up data access agreements. We thank J. Schwartzentruber, E. Steed, S. Kasela and U. Võsa for their helpful comments on the manuscript; M. Kanai, J. Ulirsch and H. Finucane for feedback on the fine-mapping workflow; and D. Gaffney for guidance in setting up this project. N.K., J.H. and J.M. were supported by a grant from Open Targets (grant no. OTAR2-046). M.P.S. and S.T. were supported by the Wellcome Trust (108749/Z/15/Z). T.B., S.J., I.P., H.P., A.Y. and D.Z. were supported by the European Molecular Biology Laboratory. K.A. was supported by the European Regional Development Fund and the program Mobilitas Pluss (MOBJD67). K.A. also received funding from the European Union’s Horizon 2020 research and innovation program (grant no. 825775) and Estonian Research Council (grant nos. IUT34-4 and PSG415). K.P. and N.K. were supported by the Estonian Research Council grant (no. PSG415). L.K. was supported by the Estonian Research Council grant (no. PSG59). K.A., N.K., K.P., I.K. and L.K. were also supported by the Estonian Centre of Excellence in ICT Research (EXCITE), funded by the European Regional Development Fund. I.K. was supported by a Distributed Infrastructure for Life-Science Information ELIXIR, European Regional Development Fund project (2014-2020.4.01.16-0271).

Publication: Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression

Citation: Võsa U, Claringbould A, Westra HJ, et al. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet. 2021;53(9):1300-1310. doi:10.1038/s41588-021-00913-z

Funding: This work is supported by a grant from the European Research Council (ERC, ERC Starting Grant agreement number 637640 ImmRisk), a VIDI grant (917.14.374) and VICI grant from the Netherlands Organisation for Scientific Research (NWO) to L.F. This work has been supported by the European Regional Development Fund and the programme Mobilitas Pluss (MOBTP108) to U.V. The project was supported by Foundation “De Drie Lichten” in the Netherlands with a grant to A.C. M.G.N. is supported by ZonMw grants 849200011 and 531003014 from The Netherlands Organisation for Health Research and Development, a VENI grant from NWO (VI.Veni.191G.030) and a Jacobs foundation research fellowship. H.Y. is funded by a Diabetes UK RD Lawrence fellowship (17/0005594). This project received funding from the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement n° 772376 - EScORIAL) to J.H.V. T.E. and A.K. were supported by the Estonian Research Council grant PRG (PRG1291). A.Ba. was supported by NIH grant 1R01MH109905, NIH grant R01HG008150 (NHGRI; Non-Coding Variants Program) and NIH grant R01MH101814 (NIH Common Fund; GTEx Program). M.v.d.W was funded by Nederlandse Organisatie voor Wetenschappelijk onderzoek, NWO-Veni 192.029. This work was supported by National Institutes of Health grants R21ES024834 (B.P. and M.A.), R01ES020506 (B.P.), R01ES023834 (B.P.), R35ES028379 (B.P.), R01 GM108711 (L.C.), and R01CA107431 (H.A.). This work was supported through The Sigrid Juselius Foundation (J.Ke.) and funds from the Academy of Finland [grant numbers 297338 and 307247] (J.Ke.) and Novo Nordisk Foundation [grant number NNF17OC0026062] (J.Ke.). S.Ri. was supported by the Academy of Finland Centre of Excellence in Complex Disease Genetics (Grant No. 312062). M.G. was supported by EU Horizon 2020 (grant 733100 for SYSCID); and grant from EOS excellence of Science (FNRS and FWO) (gnaf N° 30770923). We acknowledge support from BBMRI–NL (Biobanking and Biomolecular Resources Research Infrastructure 184.021.007 and 184.033.111); Spinozapremie (NWO- 56–464-14192), the European Research Council (ERC Advanced 230374) and KNAW Academy Professor Award (PAH/6635) to D.I.B. G.H. works in a unit that receives funding from the UK MRC (MC_UU_12013/1&2&5) and the University of Bristol. S.B. was supported by the Swiss National Science Foundation (310030–152724). This work was supported by the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept (grant # 01ZX1906B), and by LIFE – Leipzig Research Center for Civilization Diseases, Universität Leipzig (which is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by means of the Free State of Saxony within the framework of the excellence initiative to H.K. and M.Sc.

Publication: Genetic effects on gene expression across human tissues

Citation: GTEx Consortium; Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group; Statistical Methods groups—Analysis Working Group; Genetic effects on gene expression across human tissues. Nature. 2017;550(7675):204-213. doi:10.1038/nature24277

Funding: The Genotype-Tissue Expression (GTEx) project was supported by the Common Fund of the Office of the Director of the National Institutes of Health (http://commonfund.nih.gov/GTEx). Additional funds were provided by the National Cancer Institute (NCI), National Human Genome Research Institute (NHGRI), National Heart, Lung, and Blood Institute (NHLBI), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), and National Institute of Neurological Disorders and Stroke (NINDS). Donors were enrolled at Biospecimen Source Sites funded by Leidos Biomedical, Inc. (Leidos) subcontracts to the National Disease Research Interchange (10XS170) and Roswell Park Cancer Institute (10XS171). The Laboratory, Data Analysis, and Coordinating Center (LDACC) was funded through a contract (HHSN268201000029C) to The Broad Institute, Inc. Biorepository operations were funded through a Leidos subcontract to the Van Andel Institute (10ST1035). Additional data repository and project management were provided by Leidos (HHSN261200800001E). The Brain Bank was supported by a supplement to University of Miami grant DA006227. J.R.D. is supported by a Lucille P. Markey Biomedical Research Stanford Graduate Fellowship. J.R.D., Z.Z., and N.A.T. acknowledge the Stanford Genome Training Program (SGTP; NIH/NHGRI T32HG000044). Z.Z. is also supported by the National Science Foundation (NSF) GRFP (DGE-114747). L.F. is supported by the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). D.G.M. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship. D.M. is supported by NIH grants U54DK105566 and R01GM104371. B.J.S is supported by NIH training grant T32GM007057. E.K.T is supported by a Hewlett-Packard Stanford Graduate Fellowship and a doctoral scholarship from the Natural Science and Engineering Council of Canada. T.S. is supported by a National Science Foundation Graduate Research Fellowship (DGE-1656518). A.B. is supported by the Searle Scholars Program and NIH grant R01MH109905. A.B., C.D.Bu. and S.B.M are supported by NIH grant R01HG008150 (NHGRI; Non-Coding Variants Program). S.B.M. and C.D.Bu. are supported by NHGRI grants U01HG007436 and U01HG009080. A.B., C.D.Bu., E.T.D., S.E.C., T.L, and S.B.M. are supported by NIH grants R01MH101814 (NIH Common Fund; GTEx Program). C.D.Br., Y.P., B.J., G.G., and B.E.E. are supported by NIH grant R01MH101822. B.E.E. is supported by NIH grants R00HG006265, R01MH101822 and U01 HG007900 and a Sloan Faculty Fellowship. G.L., A.B.N, J.J.P., A.S., Y-H.Z., and F.A.W. are supported by NIH grants R01MH101819, R01HG009125, and R21HG007840. T.L. and P.M. are supported by NIH grant R01MH106842. T.L. is supported by the NIH grant UM1HG008901. T.L. and S.E.C. are supported by NIH contract HHSN2682010000029C. B.J. is supported by NIH grant 2T32HG003284-11. C.B.P. and C.S. are supported by NIH grant R01MH101782. D.F.C. is supported by NIH grant R01MH101810. E.R.G and N.J.C are supported by NIH grants R01MH101820 and R01MH090937A. We thank A. Nellore and C. Wilks for assistance with TCGA data, K. Small for discussions, J. T. Leek for suggestions on the manuscript, N. L. Cyr for drawing the body map in Fig. 1a, and A. Kundaje and O. Ursu for input on Hi-C analysis.

Publication: The GTEx Consortium atlas of genetic regulatory effects across human tissues

Citation: GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. 2020;369(6509):1318-1330. doi:10.1126/science.aaz1776

Funding: This work was supported by the Common Fund of the Office of the Director, U.S. National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, NIA, NIAID, and NINDS through NIH contracts HHSN261200800001E (Leidos Prime contract with NCI: A.M.S., D.E.T., N.V.R., J.A.M., L.S., M.E.B., L.Q., T.K., D.B., K.R., A.U.), 10XS170 (NDRI: W.F.L., J.A.T., G.K., A.M., S.S., R.H., G.Wa., M.J., M.Wa., L.E.B., C.J., J.W., B.R., M.Hu., K.M., L.A.S., H.M.G., M.Mo., L.K.B.), 10XS171 (Roswell Park Cancer Institute: B.A.F., M.T.M., E.K., B.M.G., K.D.R., J.B.), 10X172 (Science Care Inc.), 12ST1039 (IDOX), 10ST1035 (Van Andel Institute: S.D.J., D.C.R., D.R.V.), HHSN268201000029C (Broad Institute: F.A., G.G., K.G.A., A.V.S., X.Li., E.T., S.G., A.G., S.A., K.H.H., D.T.N., K.H., S.R.M., J.L.N.), 5U41HG009494 (F.A., G.G., K.G.A.), and through NIH grants R01 DA006227-17 (Univ. of Miami Brain Bank: D.C.M., D.A.D.), Supplement to University of Miami grant DA006227 (D.C.M., D.A.D.), R01 MH090941 (Univ. of Geneva), R01 MH090951 and R01 MH090937 (Univ. of Chicago), R01 MH090936 (Univ. of North Carolina-Chapel Hill), R01MH101814 (M.M-A., V.W., S.B.M., R.G., E.T.D., D.G-M., A.V.), U01HG007593 (S.B.M.), R01MH101822 (C.D.B.), U01HG007598 (M.O., B.E.S.), U01MH104393 (A.P.F.), extension H002371 to 5U41HG002371 (W.J.K) as well as other funding sources: R01MH106842 (T.L., P.M., E.F., P.J.H.), R01HL142028 (T.L., Si.Ka., P.J.H.), R01GM122924 (T.L., S.E.C.), R01MH107666 (H.K.I.), P30DK020595 (H.K.I.), UM1HG008901 (T.L.), R01GM124486 (T.L.), R01HG010067 (Y.Pa.), R01HG002585 (G.Wa., M.St.), Gordon and Betty Moore Foundation GBMF 4559 (G.Wa., M.St.), 1K99HG009916-01 (S.E.C.), R01HG006855 (Se.Ka., R.E.H.), BIO2015-70777-P, Ministerio de Economia y Competitividad and FEDER funds (M.M-A., V.W., R.G., D.G-M.), la Caixa Foundation ID 100010434 under agreement LCF/BQ/SO15/52260001 (D.G-M.), NIH CTSA grant UL1TR002550-01 (P.M.), Marie-Skłodowska Curie fellowship H2020 Grant 706636 (S.K-H.), R35HG010718 (E.R.G.), FPU15/03635, Ministerio de Educación, Cultura y Deporte (M.M-A.), R01MH109905, 1R01HG010480 (A.Ba.), Searle Scholar Program (A.Ba.), R01HG008150 (S.B.M.), 5T32HG000044-22, NHGRI Institutional Training Grant in Genome Science (N.R.G.), EU IMI program (UE7-DIRECT-115317-1) (E.T.D., A.V.), FNS funded project RNA1 (31003A_149984) (E.T.D., A.V.), DK110919 (F.H.), F32HG009987 (F.H.), Massachusetts Lions Eye Research Fund Grant (A.R.H.).

Publication: Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies

Citation: Lopes KP, Snijders GJL, Humphrey J, et al. Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies. Nat Genet. 2022;54(1):4-17. doi:10.1038/s41588-021-00976-y

Funding: We thank members of the Raj and de Witte labs for their feedback on the manuscript. The authors thank the teams of the Netherlands Brain Bank and the Mount Sinai Neuropathology Brain Bank and Research CoRE for their services. We thank the study participants for their generous gifts of brain donation. The microglia were isolated through the efforts of a large team and we would like to thank Manja Litjens, Roland D. van Dijk, Alba Fernández-Andreu, Paul R. Ormel, Hans C. van Mierlo, Y. He, Stephanie Gumbs, Miriam E van Strien, Saskia Burm, Vanessa Donega, and Elly M. Hol for all their contributions to this effort. The authors thank Michael Chao for his assistance with genotyping QC. This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD026880. T.R. is supported by grants from the US National Institutes of Health (NIH) NIA R21-AG063130, NIA R01-AG054005, NIA U01-AG068880, NIA RF1-AG065926, NIA R56-AG055824, and NINDS R01-NS116006. G.S. was supported through ZonMw and the foundation “De Drie Lichten” in the Netherlands. E.N. was supported by Ramon Areces fellowship. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Publication: Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease

Citation: Western D, Timsina J, Wang L, et al. Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer's disease. Nat Genet. 2024;56(12):2672-2684. doi:10.1038/s41588-024-01972-8

Funding: This work was supported by grants from the National Institutes of Health (R01AG044546 (CC), P01AG003991 (CC, JCM), RF1AG053303 (CC), RF1AG058501 (CC), U01AG058922 (CC), RF1AG074007 (YJS), R00AG062723 (LI), P30 AG066515 (TWC, MDG), the Chan Zuckerberg Initiative (CZI), the Michael J. Fox Foundation (LI, CC), the Department of Defense (LI- W81XWH2010849), the Alzheimer’s Association Zenith Fellows Award (ZEN-22-848604, awarded to CC), and the Bright Focus Foundation (A2021033S, LI). GSK provided funding to support the analyses performed in this study. The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444 (JCM), P01AG03991 (JCM), and P01AG026276 (JCM). This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the NeuroGenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/) and the Departments of Neurology and Psychiatry at Washington University School of Medicine. Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer Network (DIAN, U19AG032438) funded by the National Institute on Aging (NIA), the Alzheimer’s Association (SG-20-690363-DIAN). Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADC Olink proteomic data is part of the neurodegeneration research program of Amsterdam Neuroscience and was supported by: Alzheimer Nederland (WE.03-2018-05, MC and CT) and Selfridges Group Foundation (NR170065, MC and CT).

Publication: Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease

Citation: Yao C, Chen G, Song C, et al. Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease. Nat Commun. 2018;9(1):3268. Published 2018 Aug 15. doi:10.1038/s41467-018-05512-x

Funding: The Framingham Heart Study is funded by National Institutes of Health contract N01-HC-25195. This project was funded in part by the Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. JEH is supported in part by NIH grant K23-HL116780 and a Massachusetts General Hospital Hassenfeld Research Scholar Award. The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The KORA Study Group consists of A. Peters (speaker), J. Heinrich, R. Holle, R. Leidl, C. Meisinger, K. Strauch, and their co-workers, who are responsible for the design and conduct of the KORA studies. The INTERVAL study is funded by NHSBT (11-01-GEN) and has been supported by the NIHR-BTRU in Donor Health and Genomics (NIHR BTRU-2014-10024) at the University of Cambridge in partnership with NHSBT. This study was partially funded by Merck and Co., Kenilworth, NJ, USA. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England, or NHSBT. The MRC/BHF Cardiovascular Epidemiology Unit is supported by the UK Medical Research Council (G0800270), British Heart Foundation (SP/09/002), UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (268834), and European Commission Framework Programme 7 (HEALTH-F2-2012-279233). B.B.S. is funded by the Cambridge School of Clinical Medicine MRC/Sackler Prize PhD Studentship (MR/K50127X/1) and supported by the Cambridge School of Clinical Medicine MB-PhD programme. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. KS was supported by ‘Biomedical Research Program’ funds at Weill Cornell Medicine in Qatar, a program funded by the Qatar Foundation.

Publication: Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets

Citation: Zhao JH, Stacey D, Eriksson N, et al. Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets. Nat Immunol. 2023;24(9):1540-1551. doi:10.1038/s41590-023-01588-w

Funding: This work was performed under the auspices of the SCALLOP Consortium. We thank the following: study participants from the contributing cohorts; the International Multiple Sclerosis Genetics Consortium, which provided multiple sclerosis GWAS summary statistics used in our analyses; A. Siopi and D. McLeod for support with SCALLOP Consortium administration; the authors of the GCTA software for advice; B. Prins for help with the INTERVAL study genotype data quality control; and A. Richard for comments on the manuscript. J.E.P was supported by a grant and fellowship from the Medical Research Foundation (grant nos. MRF-042-0001-RG-PETE-C0839 and MRF-057-0003-RG-PETE-C0799). E.J.N. was supported by the Schmidt Science Fellows, in partnership with the Rhodes Trust. P.S. was supported by a Rutherford Fund Fellowship from the UK Medical Research Council (MRC; grant no. MR/S003746/1). J.D. holds a British Heart Foundation Professorship and a National Institute for Health and Care Research (NIHR) Senior Investigator Award*. C. Ha is supported by an MRC University Unit Programme Grant ‘QTL in Health and Disease’ (grant no. U.MC_UU_00007/10). Funding of the GWASs and proteomics studies of STABILITY and ARISTOTLE were supported by GlaxoSmithKline, BristolMyersSquibb and the Swedish Foundation for Strategic Research (grant no. RB13-0197). The Orkney Complex Disease Study (ORCADES) was supported by the Chief Scientist Office of the Scottish Government (grant nos. CZB/4/276 and CZB/4/710), a Royal Society University Research Fellowship to J.F.W., the MRC Human Genetics Unit quinquennial program ‘QTL in Health and Disease’, Arthritis Research UK and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). DNA extractions were performed at the Edinburgh Clinical Research Facility, University of Edinburgh. We acknowledge the invaluable contributions of the research nurses in Orkney, the administrative team in Edinburgh and the people of Orkney. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any author-accepted manuscript version arising from this submission. Participants in the INTERVAL trial were recruited with the active collaboration of National Health Service (NHS) Blood and Transplant England (www.nhsbt.nhs.uk), which has supported field work and other elements of the trial. DNA extraction and genotyping were co-funded by the NIHR, the NIHR BioResource (http://bioresource.nihr.ac.uk) and the NIHR Cambridge Biomedical Research Centre (grant no. BRC-1215-20014). The academic coordinating center for INTERVAL was supported by core funding from: the NIHR Blood and Transplant Research Unit (BTRU) in Donor Health and Genomics (grant no. NIHR BTRU-2014-10024), NIHR BTRU in Donor Health and Behaviour (grant no. NIHR203337), MRC (grant no. MR/L003120/1), British Heart Foundation (grant nos. SP/09/002, RG/13/13/30194 and RG/18/13/33946) and NIHR Cambridge BRC (grant nos. BRC-1215-20014 and NIHR203312)* and has received funding from a European Commission Innovative Medicines Initiative (BigData@Heart). The academic coordinating center thank blood donor center staff and blood donors for participating in the INTERVAL trial. This work was supported by Health Data Research UK, which is funded by the MRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. Estonian Biobank work was supported by the European Regional Development Fund and the program Mobilitas Pluss (MOBTP108, grant nos. 2014-2020.4.01.15-0012 GENTRANSMED and 2014-2020.4.01.16-0125). The present study was also funded by the EU H2020 (grant no. 692145), the Estonian Research Council (grant nos. PUT1660 and PUT PRG1291). Data analyses with Estonian datasets were carried out in part in the High-Performance Computing Center of the University of Tartu. The SWEBIC biobank was supported by the Stanley Medical Research Institute. The proteomic analyses in SWEBIC were funded by the Swedish foundation for Strategic Research (grant no. KF10-0039). For RECOMBINE and SWEBIC, the data handling and analysis were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC), partially funded by the Swedish Research Council through grant no. 2018-05973. The CROATIA-Vis study was funded by grants from the UK MRC, the Republic of Croatia Ministry of Science, Education and Sports (grant nos. 108-1080315-0302 and 216-1080315-0302) and the Croatian Science Foundation (grant no. 8875). We thank the staff of several institutions in Croatia who supported the field work, including Zagreb Medical Schools, the Institute for Anthropological Research in Zagreb, the recruitment team from the Croatian Centre for Global Health, University of Split and all the study participants. The KORA study was initiated and financed by the Helmholtz Zentrum München—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences, Ludwig-Maximilians-Universität, as part of LMUinnovativ. The measurement of inflammatory biomarkers was funded by a grant from the German Center for Diabetes Research (DZD; to C. Herder and B. Thorand). This work was also supported by the Ministry of Culture and Science of the State of North Rhine-Westphalia and the German Federal Ministry of Health. The present study was supported in part by a grant from the German Federal Ministry of Education and Research to the DZD. N.P. is supported by a Wellcome Trust Discovery award (no. 225875/Z/22/Z). D.C. is supported by the NIHR Imperial Biomedical Research Centre (BRC)*. Infrastructure support for this research was provided by the NIHR Imperial BRC. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute. We acknowledge the Danish node of the TRYGGVE server and the University of Cambridge’s High Performance Computing cluster, on which computations were performed. *The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, NHSBT or the Department of Health and Social Care.