A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

23andMe Research Team; Douglas P Wightman; Iris E Jansen; Jeanne E Savage; Alexey A Shadrin; Shahram Bahrami; Dominic Holland; Arvid Rongve; Sigrid Børte; Bendik S Winsvold; Ole Kristian Drange; Amy E Martinsen; Anne Heidi Skogholt; Cristen Willer; Geir Bråthen; Ingunn Bosnes; Jonas Bille Nielsen; Lars G Fritsche; Laurent F Thomas; Linda M Pedersen; Maiken E Gabrielsen; Marianne Bakke Johnsen; Tore Wergeland Meisingset; Wei Zhou; Petroula Proitsi; Angela Hodges; Richard Dobson; Latha Velayudhan; Julia M Sealock; Lea K Davis; Nancy L Pedersen; Chandra A Reynolds; Ida K Karlsson; Sigurdur Magnusson; Hreinn Stefansson; Steinunn Thordardottir; Palmi V Jonsson; Jon Snaedal; Anna Zettergren; Ingmar Skoog; Silke Kern; Margda Waern; Henrik Zetterberg; Kaj Blennow; Eystein Stordal; Kristian Hveem; John-Anker Zwart; Lavinia Athanasiu; Per Selnes; Ingvild Saltvedt; Dag Aarsland

doi:10.1038/s41588-021-00921-z

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

23andMe Research Team, Douglas P Wightman, Iris E Jansen, Jeanne E Savage, Alexey A Shadrin, Shahram Bahrami, Dominic Holland, Arvid Rongve, Sigrid Børte, Bendik S Winsvold, Ole Kristian Drange, Amy E Martinsen, Anne Heidi Skogholt, Cristen Willer, Geir Bråthen, Ingunn Bosnes, Jonas Bille Nielsen, Lars G Fritsche, Laurent F Thomas, Linda M PedersenMaiken E Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland Meisingset, Wei Zhou, Petroula Proitsi, Angela Hodges, Richard Dobson, Latha Velayudhan, Julia M Sealock, Lea K Davis, Nancy L Pedersen, Chandra A Reynolds, Ida K Karlsson, Sigurdur Magnusson, Hreinn Stefansson, Steinunn Thordardottir, Palmi V Jonsson, Jon Snaedal, Anna Zettergren, Ingmar Skoog, Silke Kern, Margda Waern, Henrik Zetterberg, Kaj Blennow, Eystein Stordal, Kristian Hveem, John-Anker Zwart, Lavinia Athanasiu, Per Selnes, Ingvild Saltvedt, Dag Aarsland

Research output: Contribution to journal › Article › peer-review

394 Citations (Scopus)

Abstract

Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

Original language	English
Pages (from-to)	1276-1282
Number of pages	7
Journal	Nature Genetics
Volume	53
Issue number	9
Early online date	7 Sept 2021
DOIs	https://doi.org/10.1038/s41588-021-00921-z
Publication status	Published - Sept 2021

Access to Document

10.1038/s41588-021-00921-z

Cite this

23andMe Research Team, Wightman, D. P., Jansen, I. E., Savage, J. E., Shadrin, A. A., Bahrami, S., Holland, D., Rongve, A., Børte, S., Winsvold, B. S., Drange, O. K., Martinsen, A. E., Skogholt, A. H., Willer, C., Bråthen, G., Bosnes, I., Nielsen, J. B., Fritsche, L. G., Thomas, L. F., ... Aarsland, D. (2021). A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease. Nature Genetics, 53(9), 1276-1282. https://doi.org/10.1038/s41588-021-00921-z

@article{b6811684cb2d4a02983ef39b1c023712,

title = "A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease",

abstract = "Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.",

author = "{23andMe Research Team} and Wightman, {Douglas P} and Jansen, {Iris E} and Savage, {Jeanne E} and Shadrin, {Alexey A} and Shahram Bahrami and Dominic Holland and Arvid Rongve and Sigrid B{\o}rte and Winsvold, {Bendik S} and Drange, {Ole Kristian} and Martinsen, {Amy E} and Skogholt, {Anne Heidi} and Cristen Willer and Geir Br{\aa}then and Ingunn Bosnes and Nielsen, {Jonas Bille} and Fritsche, {Lars G} and Thomas, {Laurent F} and Pedersen, {Linda M} and Gabrielsen, {Maiken E} and Johnsen, {Marianne Bakke} and Meisingset, {Tore Wergeland} and Wei Zhou and Petroula Proitsi and Angela Hodges and Richard Dobson and Latha Velayudhan and Sealock, {Julia M} and Davis, {Lea K} and Pedersen, {Nancy L} and Reynolds, {Chandra A} and Karlsson, {Ida K} and Sigurdur Magnusson and Hreinn Stefansson and Steinunn Thordardottir and Jonsson, {Palmi V} and Jon Snaedal and Anna Zettergren and Ingmar Skoog and Silke Kern and Margda Waern and Henrik Zetterberg and Kaj Blennow and Eystein Stordal and Kristian Hveem and John-Anker Zwart and Lavinia Athanasiu and Per Selnes and Ingvild Saltvedt and Dag Aarsland",

note = "Funding Information: We thank all the participants included in this study, including the participants from Finngen, GR@CE, IGAP, UKB, DemGene, TwinGene, STSA, the Gothenburg H70 Birth Cohort Studies and Clinical AD from Sweden, ANMerge, BioVU, 23andMe, HUNT, and deCODE. We thank the research participants from 23andMe who made this study possible. We thank the participants of the Norwegian Dementia Genetics Network (DemGene). This work was supported by BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (grant no. 024.004.012). This work was supported by the Research Council of Norway (RCN: 248980, 248778, 223273), Norwegian Regional Health Authorities, Norwegian Health Association (22731, EU JPND: PMI-AD RCN 311993); and National Institutes of Health, National Institute on Aging R01 AG08724, R01 AG17561, R01 AG028555 and R01 AG060470. We thank the International Genomics of Alzheimer{\textquoteright}s Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients and their families. The iSelect chips were funded by the French National Foundation on Alzheimer{\textquoteright}s disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Universit{\'e} de Lille 2 and the Lille University Hospital. GERAD/PERADES was supported by the Medical Research Council (grant no. 503480), Alzheimer{\textquoteright}s Research UK (grant no. 503176), the Wellcome Trust (grant no. 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) (grant nos. 01GI0102, 01GI0711, 01GI0420). CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01–AG–12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants U01 AG032984, U24 AG021886, U01 AG016976 and the Alzheimer{\textquoteright}s Association grant ADGC–10–196728. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = sep,

doi = "10.1038/s41588-021-00921-z",

language = "English",

volume = "53",

pages = "1276--1282",

journal = "Nature Genetics",

issn = "1061-4036",

number = "9",

}

23andMe Research Team, Wightman, DP, Jansen, IE, Savage, JE, Shadrin, AA, Bahrami, S, Holland, D, Rongve, A, Børte, S, Winsvold, BS, Drange, OK, Martinsen, AE, Skogholt, AH, Willer, C, Bråthen, G, Bosnes, I, Nielsen, JB, Fritsche, LG, Thomas, LF, Pedersen, LM, Gabrielsen, ME, Johnsen, MB, Meisingset, TW, Zhou, W, Proitsi, P , Hodges, A , Dobson, R , Velayudhan, L, Sealock, JM, Davis, LK, Pedersen, NL, Reynolds, CA, Karlsson, IK, Magnusson, S, Stefansson, H, Thordardottir, S, Jonsson, PV, Snaedal, J, Zettergren, A, Skoog, I, Kern, S, Waern, M, Zetterberg, H, Blennow, K, Stordal, E, Hveem, K, Zwart, J-A, Athanasiu, L, Selnes, P, Saltvedt, I & Aarsland, D 2021, 'A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease', Nature Genetics, vol. 53, no. 9, pp. 1276-1282. https://doi.org/10.1038/s41588-021-00921-z

TY - JOUR

T1 - A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

AU - 23andMe Research Team

AU - Wightman, Douglas P

AU - Jansen, Iris E

AU - Savage, Jeanne E

AU - Shadrin, Alexey A

AU - Bahrami, Shahram

AU - Holland, Dominic

AU - Rongve, Arvid

AU - Børte, Sigrid

AU - Winsvold, Bendik S

AU - Drange, Ole Kristian

AU - Martinsen, Amy E

AU - Skogholt, Anne Heidi

AU - Willer, Cristen

AU - Bråthen, Geir

AU - Bosnes, Ingunn

AU - Nielsen, Jonas Bille

AU - Fritsche, Lars G

AU - Thomas, Laurent F

AU - Pedersen, Linda M

AU - Gabrielsen, Maiken E

AU - Johnsen, Marianne Bakke

AU - Meisingset, Tore Wergeland

AU - Zhou, Wei

AU - Proitsi, Petroula

AU - Hodges, Angela

AU - Dobson, Richard

AU - Velayudhan, Latha

AU - Sealock, Julia M

AU - Davis, Lea K

AU - Pedersen, Nancy L

AU - Reynolds, Chandra A

AU - Karlsson, Ida K

AU - Magnusson, Sigurdur

AU - Stefansson, Hreinn

AU - Thordardottir, Steinunn

AU - Jonsson, Palmi V

AU - Snaedal, Jon

AU - Zettergren, Anna

AU - Skoog, Ingmar

AU - Kern, Silke

AU - Waern, Margda

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Stordal, Eystein

AU - Hveem, Kristian

AU - Zwart, John-Anker

AU - Athanasiu, Lavinia

AU - Selnes, Per

AU - Saltvedt, Ingvild

AU - Aarsland, Dag

N1 - Funding Information: We thank all the participants included in this study, including the participants from Finngen, GR@CE, IGAP, UKB, DemGene, TwinGene, STSA, the Gothenburg H70 Birth Cohort Studies and Clinical AD from Sweden, ANMerge, BioVU, 23andMe, HUNT, and deCODE. We thank the research participants from 23andMe who made this study possible. We thank the participants of the Norwegian Dementia Genetics Network (DemGene). This work was supported by BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (grant no. 024.004.012). This work was supported by the Research Council of Norway (RCN: 248980, 248778, 223273), Norwegian Regional Health Authorities, Norwegian Health Association (22731, EU JPND: PMI-AD RCN 311993); and National Institutes of Health, National Institute on Aging R01 AG08724, R01 AG17561, R01 AG028555 and R01 AG060470. We thank the International Genomics of Alzheimer’s Project (IGAP) for providing summary results data for these analyses. The investigators within IGAP contributed to the design and implementation of IGAP and/or provided data but did not participate in analysis or writing of this report. IGAP was made possible by the generous participation of the control subjects, the patients and their families. The iSelect chips were funded by the French National Foundation on Alzheimer’s disease and related disorders. EADI was supported by the LABEX (laboratory of excellence program investment for the future) DISTALZ grant, Inserm, Institut Pasteur de Lille, Université de Lille 2 and the Lille University Hospital. GERAD/PERADES was supported by the Medical Research Council (grant no. 503480), Alzheimer’s Research UK (grant no. 503176), the Wellcome Trust (grant no. 082604/2/07/Z) and German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) (grant nos. 01GI0102, 01GI0711, 01GI0420). CHARGE was partly supported by the NIH/NIA grant R01 AG033193 and the NIA AG081220 and AGES contract N01–AG–12100, the NHLBI grant R01 HL105756, the Icelandic Heart Association and the Erasmus Medical Center and Erasmus University. ADGC was supported by the NIH/NIA grants U01 AG032984, U24 AG021886, U01 AG016976 and the Alzheimer’s Association grant ADGC–10–196728. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

AB - Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.

UR - http://www.scopus.com/inward/record.url?scp=85114746630&partnerID=8YFLogxK

U2 - 10.1038/s41588-021-00921-z

DO - 10.1038/s41588-021-00921-z

M3 - Article

C2 - 34493870

SN - 1061-4036

VL - 53

SP - 1276

EP - 1282

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer's disease

Abstract

Access to Document

Other files and links

Fingerprint

Cite this