Risk for late-onset Alzheimer’s disease (LOAD) is driven by multiple loci primarily identified by genome-wide association studies, many of which are common variants with minor allele frequencies (MAF)> 0.01. To identify additional common and rare LOAD risk variants, we performed a GWAS on 25,170 LOAD subjects and 41,052 cognitively normal controls in 44 datasets from the International Genomics of Alzheimer’s Project (IGAP). Existing genotype data was imputed using the dense, high-resolution Haplotype Reference Consortium (HRC) r1.1 reference panel. Stage 1 associations of P <10−5 were meta-analyzed with the European Alzheimer’s Disease Biobank (EADB) (n=20,301 cases; 21,839 controls) (stage 2 combined IGAP and EADB). An expanded meta-analysis was performed using a GWAS of parental AD/dementia history in the UK Biobank (UKBB) (n=35,214 cases; 180,791 controls) (stage 3 combined IGAP, EADB, and UKBB). Common variant (MAF≥0.01) associations were identified for 29 loci in stage 2, including novel genome-wide significant associations at TSPAN14 ( P =2.33×10−12), SHARPIN ( P =1.56×10−9), and ATF5/SIGLEC11 ( P =1.03×10−8), and newly significant associations without using AD proxy cases in MTSS1L/IL34 ( P =1.80×10−8), APH1B ( P =2.10×10−13), and CLNK ( P =2.24×10−10). Rare variant (MAF<0.01) associations with genome-wide significance in stage 2 included multiple variants in APOE and TREM2 , and a novel association of a rare variant (rs143080277; MAF=0.0054; P =2.69×10−9) in NCK2 , further strengthened with the inclusion of UKBB data in stage 3 ( P =7.17×10−13). Single-nucleus sequence data shows that NCK2 is highly expressed in amyloid-responsive microglial cells, suggesting a role in LOAD pathology. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement ADGC. The National Institutes of Health, National Institute on Aging (NIH-NIA) supported this work through the following grants: ADGC, U01 AG032984, RC2 AG036528; Samples from the National Cell Repository for Alzheimer’s Disease (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible; Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689); GCAD, U54 AG052427; NACC, U01 AG016976; NIA LOAD (Columbia University), U24 AG026395, U24 AG026390, R01AG041797; Banner Sun Health Research Institute P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG048927, R01AG33193, R01 AG009029; Columbia University, P50 AG008702, R37 AG015473, R01 AG037212, R01 AG028786; Duke University, P30 AG028377, AG05128; Emory University, AG025688; Group Health Research Institute, UO1 AG006781, UO1 HG004610, UO1 HG006375, U01 HG008657; Indiana University, P30 AG10133, R01 AG009956, RC2 AG036650; Johns Hopkins University, P50 AG005146, R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574, R01 AG032990, KL2 RR024151; Mount Sinai School of Medicine, P50 AG005138, P01 AG002219; New York University, P30 AG08051, UL1 RR029893, 5R01AG012101, 5R01AG022374, 5R01AG013616, 1RC2AG036502, 1R01AG035137; North Carolina A&T University, P20 MD000546, R01 AG28786-01A1; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017, R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG030146, R01 AG01101, RC2 AG036650, R01 AG22018; TGen, R01 NS059873; University of Alabama at Birmingham, P50 AG016582; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501, P01 AG019724; University of Kentucky, P30 AG028383, AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133, AG030653, AG041718, AG07562, AG02365; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, AG019757; University of Washington, P50 AG005136, R01 AG042437; University of Wisconsin, P50 AG033514; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681, P01 AG03991, P01 AG026276; FTLD-TDP GWAS: P01 AG101024, P01 AG06659, and P01 AG017586). Additional analysis support was funded by R01 AG054060 at the University of Pennsylvania, and PrediXcan analysis was supported by RF1 AG061351 at Vanderbilt University Medical Center, Case-Western Reserve University, and the University of Pennsylvania. The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by NINDS grant # NS39764, NIMH MH60451 and by Glaxo Smith Kline. Support was also from the Alzheimer's Association (LAF, IIRG-08-89720; MP-V, IIRG-05-14147), the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program, and BrightFocus Foundation (MP-V, A2111048). P.S.G.-H. is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. Genotyping of the TGEN2 cohort was supported by Kronos Science. The TGen series was also funded by NIA grant AG041232 to AJM and MJH, The Banner Alzheimer's Foundation, The Johnnie B. Byrd Sr. Alzheimer's Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local NHS trusts and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council),South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England (HEFCE), Alzheimer's Research Trust (ART), BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), The Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, Brain Net Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, Universitat de Barcelona. ADNI data collection and sharing was funded by the National Institutes of Health Grant U01 AG024904 and Department of Defense award number W81XWH-12-2-0012. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ([www.fnih.org][1]). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Matthias Riemenschneider was funded by the BMBF NGFN Grant 01GS08125. Funding for Saarland University was provided by the German Federal Ministry of Education and Research (BMBF), grant number 01GS08125 to Matthias Riemenschneider. We thank Drs. D. Stephen Snyder, Alison Yao, and Marilyn Miller from NIA who are ex-officio ADGC members. EADI. This work has been developed and supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimers disease) including funding from MEL (Metropole europenne de Lille), ERDF (European Regional Development Fund) and Conseil Rgional Nord Pas de Calais. This work was supported by INSERM, the National Foundation for Alzheimers disease and related disorders, the Institut Pasteur de Lille and the Centre National de Recherche en Gnomique Humaine, CEA, the JPND PERADES, the Laboratory of Excellence GENMED (Medical Genomics) grant no. ANR10LABX0013 managed by the National Research Agency (ANR) part of the Investment for the Future program, and the FP7 AgedBrainSysBio. The ThreeCity Study was performed as part of collaboration between the Institut National de la Sant et de la Recherche Mdicale (Inserm), the Victor Segalen Bordeaux II University and SanofiSynthlabo. The Fondation pour la Recherche Mdicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salaris, Direction Generale de la Sant, MGEN, Institut de la Longvit, Agence Francaise de Scurit Sanitaire des Produits de Sant, the Aquitaine and Bourgogne Regional Councils, Agence Nationale de la Recherche, ANR supported the COGINUT and COVADIS projects. Fondation de France and the joint French Ministry of Research/ INSERM Cohortes et collections de donnes biologiques programme. Lille Gnopole received an unconditional grant from Eisai. The ThreeCity biological bank was developed and maintained by the laboratory for genomic analysis LAGBRC Institut Pasteur de Lille. CHARGE. Infrastructure for the CHARGE Consortium is supported in part by National Heart, Lung, and Blood Institute grant HL105756 (Psaty) and RC2HL102419 (Boerwinkle) and the neurology working group by grants from the National Institute on Aging, R01 AG033193, U01 AG049505 and U01 AG52409. Rotterdam (RS). This study was funded by the Netherlands Organisation for Health Research and Development (ZonMW) as part of the Joint Programming for Neurological Disease (JPND) as part of the PERADES Program (Defining Genetic Polygenic, and Environmental Risk for Alzheimer's disease using multiple powerful cohorts, focused Epigenetics and Stem cell metabolomics), Project number 733051021. This work was funded also by the European Union Innovative Medicine Initiative (IMI) programme under grant agreement No. 115975 as part of the Alzheimer's Disease Apolipoprotein Pathology for Treatment Elucidation and Development (ADAPTED, );and the European Union's Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer's disease CoSTREAM project ([www.costream.eu][2], grant agreement No. 667375). The current study is supported by the Deltaplan Dementie and Memorabel supported by ZonMW (Project number 733050814) and Alzheimer Nederland. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study (RS-I, RS-II, RS-III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS datasets are supported by the Netherlands Organization of Scientific Research NWO Investments (Project number 175.010.2005.011, 911-03-012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA), project number 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters, MSc, and Carolina Medina-Gomez, MSc, for their help in creating the GWAS database, and Karol Estrada, PhD, Yurii Aulchenko, PhD, and Carolina Medina-Gomez, MSc, for the creation and analysis of imputed data. AGES. The AGES study has been funded by NIA contracts N01-AG-12100 and HHSN271201200022C with contributions from NEI, NIDCD, and NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). Cardiovascular Health Study (CHS). This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grant U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG033193, R01AG023629, R01AG15928, and R01AG20098 and by U01AG049505 from the National Institute on Aging (NIA). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. A full list of CHS principal investigators and institutions can be found at . The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. Framingham Heart Study (FHS). This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contracts N01-HC-25195 and HHSN268201500001I). This study was also supported by grants from the National Institute on Aging: R01AG033193, U01AG049505, U01AG52409, R01AG054076 (S. Seshadri). S. Seshadri and A.L.D. were also supported by additional grants from the National Institute on Aging (R01AG049607, R01AG033040) and the National Institute of Neurological Disorders and Stroke (R01- NS017950, NS100605). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institutes of Health. Atherosclerosis Risk in Communities Study (ARIC). The research is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694 and R01HL7825; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Funds for this project were also supported by grant HL093029 to MF. GERAD/PERADES. We thank all individuals who participated in this study. Cardiff University was supported by the Wellcome Trust, Alzheimer's Society (AS; grant RF014/164), the Medical Research Council (MRC; grants G0801418/1, MR/K013041/1, MR/L023784/1), the European Joint Programme for Neurodegenerative Disease (JPND, grant MR/L501517/1), Alzheimer's Research UK (ARUK, grant ARUK-PG2014-1), Welsh Assembly Government (grant SGR544:CADR), a donation from the Moondance Charitable Foundation, UK Dementia's Platform (DPUK, reference MR/L023784/1), and the UK Dementia Research Institute at Cardiff. Cambridge University acknowledges support from the MRC. ARUK supported sample collections at the Kings College London, the South West Dementia Bank, Universities of Cambridge, Nottingham, Manchester and Belfast. King's College London was supported by the NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and Kings College London and the MRC. Alzheimer's Research UK (ARUK) and the Big Lottery Fund provided support to Nottingham University. Ulster Garden Villages, AS, ARUK, American Federation for Aging Research, NI R&D Office and the Royal College of Physicians/Dunhill Medical Trust provided support for Queen's University, Belfast. The University of Southampton acknowledges support from the AS. The MRC and Mercer's Institute for Research on Ageing supported the Trinity College group. DCR is a Wellcome Trust Principal Research fellow. The South West Dementia Brain Bank acknowledges support from Bristol Research into Alzheimer's and Care of the Elderly. The Charles Wolfson Charitable Trust supported the OPTIMA group. Washington University was funded by NIH grants, Barnes Jewish Foundation and the Charles and Joanne Knight Alzheimer's Research Initiative. Patient recruitment for the MRC Prion Unit/UCL Department of Neurodegenerative Disease collection was supported by the UCLH/UCL Biomedical Research Centre and their work was supported by the NIHR Queen Square Dementia BRU, the Alzheimer's Research UK and the Alzheimer's Society. LASER-AD was funded by Lundbeck SA. The AgeCoDe study group was supported by the German Federal Ministry for Education and Research grants 01 GI 0710, 01 GI 0712, 01 GI 0713, 01 GI 0714, 01 GI 0715, 01 GI 0716, 01 GI 0717. Genotyping of the Bonn case-control sample was funded by the German centre for Neurodegenerative Diseases (DZNE), Germany. The GERAD Consortium also used samples ascertained by the NIMH AD Genetics Initiative. HH was supported by a grant of the Katharina-Hardt-Foundation, Bad Homburg vor der Höhe, Germany. The KORA F4 studies were financed by Helmholtz Zentrum München; German Research Center for Environmental Health; BMBF; German National Genome Research Network and the Munich Center of Health Sciences. The Heinz Nixdorf Recall cohort was funded by the Heinz Nixdorf Foundation (Dr. Jur. G.Schmidt, Chairman) and BMBF. We acknowledge use of genotype data from the 1958 Birth Cohort collection and National Blood Service, funded by the MRC and the Wellcome Trust which was genotyped by the Wellcome Trust Case Control Consortium and the Type-1 Diabetes Genetics Consortium, sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development and Juvenile Diabetes Research Foundation International. The project is also supported through the following funding organisations under the aegis of JPND - [www.jpnd.eu][3] (United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)) and through the Motor Neurone Disease Association. This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Prof Jens Wiltfang is supported by an Ilídio Pinho professorship and iBiMED (UID/BIM/04501/2013), at the University of Aveiro, Portugal. The Bonn Study. The Bonn samples are part of the German Dementia Competance Network (DCN) and the German Research Network on Degenerative Dementia (KNDD), which are funded by the German Federal Ministry of Education and Research (grants KND: 01G10102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 04GI0434; grants KNDD: 01GI1007A, 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716, 01ET1006B). Part of the work was funded by the JPND EADB grant (German Federal Ministry of Education and Research (BMBF) grant: 01ED1619A). This group would like to thank Dr. Heike Koelsch for her scientific support. Markus M Nothen is a member of the German Research Foundation (DFG) cluster of excellence ImmunoSensation. EADB. We thank the numerous participants, researchers, and staff from many studies who collected and contributed to the data. We thank the high-performance computing service of the University of Lille. We thank all the CEA-CNRGH staff who contributed to sample preparation and genotyping for their excellent technical assistance. This research has been conducted using the UK Biobank Resource under Application Number 61054. This work was supported by a grant (European Alzheimer DNA BioBank, EADB) from the EU Joint Programme, Neurodegenerative Disease Research (JPND). Inserm UMR1167 is also funded by Inserm, Institut Pasteur de Lille, the Lille Metropole Communaute Urbaine, the French government LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to Alzheimer disease). Additional support for EADB cohorts was provided by. Italian Ministry of Health (Ricerca Corrente); Ministero dell Istruzione, dell Universita e della Ricerca MIUR project Dipartimenti di Eccellenza 2018 2022 to Department of Neuroscience Rita Levi Montalcini, University of Torino (IR), and AIRAlzh Onlus ANCCCOOP (SB); Partly supported by Ministero della Salute, I.R.C.C.S. Research Program, Ricerca Corrente 2018 2020, Linea n. 2 Meccanismi genetici, predizione e terapie innovative delle malattie complesse and by the 5 x 1000 voluntary contribution to the Fondazione I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza; and RF 2018 12366665, Fondi per la ricerca 2019 (Sandro Sorbi). Copenhagen General Population Study (CGPS). We thank staff and participants of the CGPS for their important contributions. Karolinska Institutet AD cohort. Dr. Graff and coauthors of the Karolinska Institutet AD cohort report grants from Swedish Research Council (VR) 2015 02926, 2018 02754, 2015 06799, Swedish Alzheimer Foundation, Stockholm County Council ALF and research school, Karolinska Institutet StratNeuro, Swedish Demensfonden, and Swedish brain foundation, during the conduct of the study. ADGEN: This work was supported by Academy of Finland (grant numbers 307866); Sigrid Juselius Foundation; the Strategic Neuroscience Funding of the University of Eastern Finland; EADB project in the JPNDCOFUND program (grant number 301220). CBAS. Supported by the project no. LQ1605 from the National Program of Sustainability II (MEYS CR), Supported by Ministry of Health of the Czech Republic, grant nr. NV190400270 (All rights reserved), Grant Agency of Charles University Grants No. 693018 and 654217; the Ministry of Health, Czech Republic―conceptual development of research organization, University Hospital Motol, Prague, Czech Republic Grant No. 00064203; the Czech Ministry of Health Project AZV Grant No. 16―27611A; and Institutional Support of Excellence 2. LF UK Grant No. 699012. CNRMAJ Rouen. This study received fundings from the Centre National de Référence Malades Alzheimer Jeunes (CNRMAJ). The Finnish Geriatric Intervention Study for the Prevention of Cognitive Impairment and Disability (FINGER). Data collection was supported by grants from the Academy of Finland, La Carita Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture Research Grants, Yrjo Jahnsson Foundation, Finnish Cultural Foundation South Ostrobothnia Regional Fund, and EVO/State Research Funding grants of University Hospitals of Kuopio, Oulu and Turku, Seinajoki Central Hospital and Oulu City Hospital, Alzheimer Research & Prevention Foundation USA, AXA Research Fund, Knut and Alice Wallenberg Foundation Sweden, Center for Innovative Medicine (CIMED) at Karolinska Institutet Sweden, and Stiftelsen Stockholms sjukhem Sweden. FINGER cohort genotyping was funded by EADB project in the JPND COFUND (grant number 301220). Belgian EADB cohort. Research is funded in part by the Alzheimer Research Foundation (SAOFRA), The Research Foundation Flanders (FWO), and the University of Antwerp Research Fund. FK is supported by a BOF DOCPRO fellowship of the University of Antwerp Research Fund. SNACK is financially supported by the Swedish Ministry of Health and Social Affairs, the participating County Councils and Municipalities, and the Swedish Research Council. BDR Bristol. We would like to thank the South West Dementia Brain Bank (SWDBB) for providing brain tissue for this study. The SWDBB is part of the Brains for Dementia Research programme, jointly funded by Alzheimers Research UK and Alzheimer Society and is supported by BRACE (Bristol Research into Alzheimers and Care of the Elderly) and the Medical Research Council. BDR Manchester. We would like to thank the Manchester Brain Bank for providing brain tissue for this study. The Manchester Brain Bank is part of the Brains for Dementia Research programme, jointly funded by Alzheimers Research UK and Alzheimers Society. BDR KCL. Human postmortem tissue was provided by the London Neurodegenerative Diseases Brain Bank which receives funding from the UK Medical Research Council and as part of the Brains for Dementia Research programme, jointly funded by Alzheimer Research UK and the Alzheimers Society. CFAS Wales. This study was funded by the ESRC (RES060250060) and HEFCW as Maintaining function and wellbeing in later life: a longitudinal cohort study, (Principal Investigators: R.T. Woods, L. Clare, G. Windle, V. Burholt, J. Philips, C. Brayne, C. McCracken, K. Bennett, F. Matthews). MRC. Cardiff University was supported by the Alzheimer Society (AS; grant RF014/164) and the Medical Research Council (MRC; grants G0801418/1, MR/K013041/1, MR/L023784/1) (R. Sims is an AS Research Fellow). Cardiff University was also supported by the European Joint Programme for Neurodegenerative Disease (JPND; grant MR/L501517/1), Alzheimer Research UK (ARUK; grant ARUKPG20141), the Welsh Assembly Government (grant SGR544:CADR), Brain for dementia Research and a donation from the Moondance Charitable Foundation. Patient recruitment for the MRC Prion Unit/UCL Department of Neurodegenerative Disease collection was supported by the UCLH/UCL Biomedical Centre and NIHR Queen Square Dementia Biomedical Research Unit. The University of Southampton acknowledges support from the AS. King College London was supported by the NIHR Biomedical Research Centre for Mental Health and the Biomedical Research Unit for Dementia at the South London and Maudsley NHS Foundation Trust and by King College London and the MRC. ARUK and the Big Lottery Fund provided support to Nottingham University. German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe). This study/publication is part of the German Research Network on Dementia (KND), the German Research Network on Degenerative Dementia (KNDD; German Study on Ageing, Cognition and Dementia in Primary Care Patients; AgeCoDe), and the Health Service Research Initiative (Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest old primary care patients (85+; AgeQualiDe)) and was funded by the German Federal Ministry of Education and Research (grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434; grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716; grants Health Service Research Initiative: 01GY1322A, 01GY1322B, 01GY1322C, 01GY1322D, 01GY1322E, 01GY1322F, 01GY1322G). VITA study. The support of the Ludwig Boltzmann Society and the AFI Germany have supported the VITA study. This work was financed by a research grant of the Vogelstiftung Dr. Eckernkamp. HELIAD study. This study was supported by the grants: IIRG09133014 from the Alzheimer Association, 189 10276/8/9/2011 from the ESPAEU program Excellence Grant (ARISTEIA) and the 51657/14.4.2009 of the Ministry for Health and Social Solidarity (Greece). Biobank Department of Psychiatry, UMG. Prof. Jens Wiltfang is supported by an Ildio Pinho professorship and iBiMED (UID/BIM/04501/2013), and FCT project PTDC/DTP\_PIC/5587/2014 at the University of Aveiro, Portugal. Lausanne study. This work was supported by grants from the Swiss National Research Foundation (SNF 320030\_141179). PAGES study: Harald Hampel is an employee of Eisai Inc. During part of this work, he was supported by the AXA Research Fund, the Fondation partenariale Sorbonne Universit and the Fondation pour la Recherche sur Alzheimer, Paris, France. Mannheim, Germany Biobank. Department of geriatric Psychiatry, Central Institute for Mental Health, Mannheim, University of Heidelberg, Germany. Swedish Twin Studies of Aging. Genotyping was supported by NIH/NIA grant R01 AG037985. Genotyping in TwinGene was supported by NIH/NIDDK U01 DK066134. WvdF is recipient of Joint Programming for Neurodegenerative Diseases (JPND) grants PERADES (ANR13JPRF0001) and EADB (733051061). Gothenburg Birth Cohort (GBC) Studies. We would like to thank UCL Genomics for performing the genotyping analyses. The studies were supported by The Stena Foundation, The Swedish Research Council (201502830, 20138717), The Swedish Research Council for Health, Working Life and Wellfare (20131202, 20050762, 20081210, 20132300, 2013 2496, 20130475), The Brain Foundation, Sahlgrenska University Hospital (ALF), The Alzheimer Association (IIRG036168), The Alzheimers Association Zenith Award (ZEN013151), Eivind och Elsa K:son Sylvans Stiftelse, The Swedish Alzheimer Foundation. Clinical AD, Sweden: We would like to thank UCL Genomics for performing the genotyping analyses. Barcelona Brain Biobank: Brain Donors of the Neurological Tissue Bank of the Biobanc Hospital Clinic IDIBAPS and their families for their generosity. Hospital Clinic de Barcelona Spanish Ministry of Economy and Competitiveness Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, Una manera de hacer Europa grants (PI16/0235 to Dr. R. SanchezValle and PI17/00670 to Dr. A. Antonell). AA is funded by Departament de Salut de la Generalitat de Catalunya, PERIS 20162020 (SLT002/16/00329). Sydney Memory and Ageing Study (Sydney MAS). We gratefully acknowledge and thank the following for their contributions to Sydney MAS: participants, their supporters and the Sydney MAS Research Team (current and former staff and students). Funding was awarded from the Australian National Health and Medical Research Council (NHMRC) Program Grants (350833, 568969, 109308). AddNeuroMed consortium. This was led by Simon Lovestone, Bruno Vellas, Patrizia Mecocci, Magda Tsolaki, Iwona Kłoszewska, Hilkka Soininen. This work was supported by InnoMed (Innovative Medicines in Europe), an integrated project funded by the European Union of the Sixth Framework program priority (FP62004 LIFESCIHEALTH5). Oviedo. This work was partly supported by Grant from Fondo de Investigaciones Sanitarias Fondos FEDER European Union to Victoria Alvarez PI15/00878. Pascual Sanchez-Juan is supported by CIBERNED and Carlos III Institute of Health, Spain (PI08/0139, PI12/02288, and PI16/01652), jointly funded by Fondo Europeo de Desarrollo Regional (FEDER), Union Europea, Una manera de hacer Europa. Project MinE. The ProjectMinE study was supported by the ALS Foundation Netherlands and the MND association (UK) (Project MinE, [www.projectmine.com][4]). The SPIN cohort. We are indebted to patients and their families for their participation in the Sant Pau Initiative on Neurodegeneration cohort, at the Sant Pau Hospital (Barcelona). This is a multimodal research cohort for biomarker discovery and validation that is partially funded by Generalitat de Catalunya (2017 SGR 547 to JC), as well as from the Institute of Health Carlos III Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDER Una manera de Hacer Europa) (grants PI11/02526, PI14/01126, and PI17/01019 to JF; PI17/01895 to AL), and the Centro de Investigacion Biomdica en Red Enfermedades Neurodegenerativas programme (Program 1, Alzheimer Disease to AL). We would also like to thank the Fundacio Bancaria Obra Social La Caixa (DABNI project) to JF and AL; and Fundacion BBVA (to AL), for their support in funding this followup study. Adolfo Lopez de Munain is supported by Fundacion Salud 2000 (PI2013156) and Diputacion Foral de Gipuzkoa (Exp.114/17). GR@ACE/DEGESCO. We would like to thank patients and controls who participated in this project. Genome Resesarch @ Fundació ACE project (GR@ACE) is supported by Fundación bancaria La Caixa, Grifols SA, Fundació ACE and ISCIII. We also want to thank other private sponsors supporting the basic and clinical projects of our institution (Piramal AG, Laboratorios Echevarne, Araclon Biotech S.A. and Fundació ACE). We are indebted to Trinitat Port-Carbó legacy and her family for their support of Fundació ACE research programs. Fundació ACE collaborates with the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain) and is one of the participating centers of the Dementia Genetics Spanish Consortium (DEGESCO). A.R. and M.B. receive support from the European Union/EFPIA Innovative Medicines Initiative Joint undertaking ADAPTED and MOPEAD projects (grant numbers 115975 and 115985, respectively). M.B. and A.R. are also supported by national grants PI13/02434, PI16/01861, PI17/01474 and PI19/01240. Accion Estratgica en Salud is integrated into the Spanish National R + D + I Plan and funded by ISCIII (Instituto de Salud Carlos III) Subdireccion General de Evaluacion and the Fondo Europeo de Desarrollo Regional (FEDERUna manera de hacer Europa). Some control samples and data from patients included in this study were provided in part by the National DNA Bank Carlos III ([www.bancoadn.org][5], University of Salamanca, Spain) and Hospital Universitario Virgen de Valme (Sevilla, Spain); they were processed following standard operating procedures with the appropriate approval of the Ethical and Scientific Committee. The present work has been performed as part of the doctoral program of I. de Rojas at the Universitat de Barcelona (Barcelona, Spain). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: All protocols used by this study have been approved by the Institutional Review Board (IRB) at the University of Pennsylvania and all participating institutions. All subjects have been consented for participation in genetic studies and all data is human subjects research exempted as only de-identified data were used in analysis. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Summary statistics will be made available upon publication. Original genotype and phenotype data may be made available upon request through study principal investigators and/or controlled-access genetics data repositories- see individual dataset descriptions for additional details. All the data used in the gene prioritization are publically available: GTEx pipeline: GTEx v8 eQTL and sQTL catalogues: GTEx v8 expression and splicing prediction models: [1]: http://www.fnih.org [2]: http://www.costream.eu [3]: http://www.jpnd.eu [4]: http://www.projectmine.com [5]: http://www.bancoadn.org