Genetic risk factors underlying white matter hyperintensities and cortical atrophy

3112 Neurotieteet

This study was funded by the National Institutes of Health (R01AG056726, P30 AG066546, NS017950, and AG059421). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (75N92022D00001, 75N92022D00002, 75N92022D00003, 5N92022D00004, 75N92022D00005). The ARIC Neurocognitive Study is supported by U01HL096812, U01HL096814, U01HL096899, U01HL096902, and U01HL096917 from the National Institutes of Health (NHLBI, NINDS, NIA and NIDCD). The authors thank the staff and participants of the ARIC study for their important contributions. The MEMENTO cohort is sponsored by Bordeaux University Hospital (coordination: CIC1401-EC, Bordeaux) and was funded through research grants from the Foundation Plan Alzheimer (Alzheimer Plan 2008–2012), the French Ministry of Research and Higher Education (Plan Maladies Neurodégénératives (2016–2019)). Computations were performed on the Bordeaux Bioinformatics Centre computer resources, University of Bordeaux. Funding support for additional computer resources at the CREDIM, University of Bordeaux, has been provided to Dr Debette by the Fondation Claude Pompidou. The Three-City (3 C) Study is conducted under a partnership agreement among the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, and Sanofi-Aventis. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3 C Study is also supported by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, Mutuelle Générale de l’Education Nationale (MGEN), Institut de la Longévité, Conseils Régionaux of Aquitaine and Bourgogne, Fondation de France, and Ministry of Research–INSERM Programme “Cohortes et collections de données biologiques.” This work is supported by France 2030 with a grant overseen by the French National Research Agency (ANR) ANR-18-RHUS-0002 and the IHU Precision and Global Vascular Brain Health Institute (ANR-23-IAHU-0001), and the BRIDGET JPND project, with funding from the EU Horizon 2020 research and innovation programme under grant agreements 643417, 640643, 667375, and 754517. It also received support from a grant (EADB) from the EU Joint Programme - Neurodegenerative Disease Research, the National Foundation for Alzheimer’s Disease and Related Disorders, the Institut Pasteur de Lille, the Labex DISTALZ, and the Centre National de Recherche en Génomique Humaine. LIFE-Adult is funded by the Leipzig Research Centre for Civilisation Diseases (LIFE). LIFE is an organisational unit affiliated to the Medical Faculty of the University of Leipzig. LIFE is funded by means of the European Union, by the European Regional Development Fund (ERDF) and by funds of the Free State of Saxony within the framework of the excellence initiative. The FinnGen project is funded by two grants from Business Finland (HUS 4685/31/2016 and UH 4386/31/2016) and the following industry partners: AbbVie Inc., AstraZeneca UK Ltd, Biogen MA Inc., Bristol Myers Squibb (and Celgene Corporation & Celgene International II Sàrl), Genentech Inc., Merck Sharp & Dohme LCC, Pfizer Inc., GlaxoSmithKline Intellectual Property Development Ltd., Sanofi US Services Inc., Maze Therapeutics Inc., Janssen Biotech Inc, Novartis AG, and Boehringer Ingelheim International GmbH. . E.S. is supported by the Research Council of Finland (338229).

The summary statistics from the meta-GWAS generated in this study have been deposited in the following database: https://figshare.com/articles/dataset/White_matter_hyperintensities_and_cortical_atrophy_genetic_risk_factors_and_underlying_neurobiology/27038320. Allen Human Brain Atlas gene expression, as parcellated in the Desikan-Killiany atlas is shared here: https://figshare.com/articles/dataset/Cell-specific_gene-expression_profiles_and_cortical_thickness_in_the_human_brain/4752955. Allen Human multiple cortical snRNAseq data was downloaded from here: https://portal.brain-map.org/atlases-and-data/rnaseq/human-multiple-cortical-areas-smart-seq. GWAS for plasma protein levels were downloaded from: https://www.synapse.org/Synapse:syn51364943/wiki/. Source Data are provided as a source data file. Source data are provided in this paper.

Following biobanks are acknowledged for delivering biobank samples to FinnGen: Auria Biobank (www.auria.fi/biopankki), THL Biobank (www.thl.fi/biobank), Helsinki Biobank (www.helsinginbiopankki.fi), Biobank Borealis of Northern Finland (https://www.ppshp.fi/Tutkimus-ja-opetus/Biopankki/Pages/Biobank-Borealis-briefly-in-English.aspx), Finnish Clinical Biobank Tampere (www.tays.fi/en-US/Research_and_development/Finnish_Clinical_Biobank_Tampere), Biobank of Eastern Finland (www.ita-suomenbiopankki.fi/en), Central Finland Biobank (www.ksshp.fi/fi-FI/Potilaalle/Biopankki), Finnish Red Cross Blood Service Biobank (www.veripalvelu.fi/verenluovutus/biopankkitoiminta), Terveystalo Biobank (www.terveystalo.com/fi/Yritystietoa/Terveystalo-Biopankki/Biopankki/) and Arctic Biobank (https://www.oulu.fi/en/university/faculties-and-units/faculty-medicine/northern-finland-birth-cohorts-and-arctic-biobank). All Finnish Biobanks are members of BBMRI.fi infrastructure (https://www.bbmri-eric.eu/national-nodes/finland/). Finnish Biobank Cooperative -FINBB (https://finbb.fi/) is the coordinator of BBMRI-ERIC operations in Finland. The Finnish biobank data can be accessed through the Fingenious® services (https://site.fingenious.fi/en/) managed by FINBB.