This is a preprint.
It has not yet been peer reviewed by a journal.
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[Preprint]. 2025 May 9:2025.05.07.25327065.
doi: 10.1101/2025.05.07.25327065.
APOE stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease
Jesper Qvist Thomassen
1
, Leonard Hampton
2
, Brittany Ulms
3
, Benjamin Grenier-Boley
4
, Sami Heikkinen
5
, Pablo Garcia
6
, Atahualapa Castillo-Morales
7
, Masataka Kikuchi
8
, Jungsoo Gim
9
10
11
12
, Han Cao
13
14
, Fahri Küçükali
15
16
, Najaf Amin
3
, Dabin Yoon
9
10
, Itziar de Rojas
6
17
18
, Pilar Alvarez Jerez
2
, Victoria Alvarez
19
20
, Beatrice Arosio
21
22
, Celine Bellenguez
4
, Sverre Bergh
23
24
, Kimberly Billingsley
2
, Cornelis Blauwendraat
25
, Merce Boada
6
17
, Barbara Borroni
26
27
, Paola Bossù
28
, María J Bullido
17
29
30
, Antonio Daniele
31
32
, Ángel Carracedo
33
34
, Alexandre de Mendonça
35
, Mark Cookson
2
, Jürgen Deckert
36
, Martin Dichgans
37
38
39
, Srdjan Djurovic
40
41
, Oriol Dols-Icardo
17
42
, Carole Dufouil
43
, Emrah Düzel
44
45
, Valentina Escott-Price
46
, Tormod Fladby
47
48
, Laura Fratiglioni
49
50
, Amy K Y Fu
13
14
51
52
, Daniela Galimberti
53
54
, Jose Maria García-Alberca
2
17
, Vilmantas Giedraitis
55
, Guillermo Garcia-Ribas
56
, Caroline Graff
49
50
, Timo Grimmer
57
, Edna Grünblatt
58
59
60
, OIivier Hanon
61
, Lucrezia Hausner
62
, Stefanie Heilmann-Hemibach
63
, Jakub Hort
64
65
, Frank Jessen
66
67
68
, Kendall Jensen
69
, Caroline Jonson
2
, Yoontae Kim
10
11
, Nicole Kuznetsov
2
, Ville Leinonen
70
71
, Anssi Lipponen
5
, Jiao Luo
1
72
, Mary Makarious
2
, Henna Martiskainen
5
, Carlo Masullo
73
, Patrizia Mecocci
74
75
, Shima Mehrabian
76
, Pablo Mir
17
77
78
, Akinori Miyashita
8
, Susanne Moebus
79
, Kin Y Mok
13
14
80
, Laura Molina Porcel
81
82
, Fermin Moreno
17
83
84
, Benedetta Nacmias
85
86
, Lucilla Parnetti
87
, Pau Pastor
88
89
, Jordi Pérez-Tur
17
90
, Oliver Peters
91
92
, Yolande A L Pijnenburg
93
94
, Gerard Piñol-Ripoll
95
96
, Julius Popp
97
98
99
, Innocenzo Rainero
100
, Luis M Real
101
102
, Steffi Riedel-Heller
103
, Eloy Rodriguez-Rodriguez
17
104
, Arvid Rongve
105
, Giacomina Rossi
106
, Jose Luis Royo
102
, Dan Rujescu
107
108
, Ingvild Saltvedt
109
, María Eugenia Sáez
110
, Raquel Sánchez-Valle
111
, Florentino Sanchez-Garcia
112
, Nicolai Sandau
1
, Nikolaos Scarmeas
113
114
, Katja Scheffler
109
115
, Norbert Scherbaum
116
, Anja Schneider
67
117
, Geir Selbæk
118
119
120
, Davide Seripa
121
, Vincenzo Solfrizzi
122
123
, Marco Spallazzi
124
, Alessio Squassina
125
, Eystein Stordal
126
, Niccoló Tesi
94
127
128
, Lucio Tremolizzo
129
130
, Kumar P Tripathi
131
132
, Wiesje M van der Flier
93
94
133
, Julie Williams
7
134
, Jens Wiltfang
135
136
137
, Dag Aarsland
138
139
140
, Andrew B Singleton
2
, Philippe Amouyel
4
, Stéphanie Debette
43
, Gael Nicolas
141
, Sven van der Lee
93
94
127
, Henne Holstege
93
94
127
142
143
, Maria Victoria Fernandez
6
, Patrick Gavin Kehoe
144
, Kristel Sleegers
15
16
, Martin Ingelsson
55
145
146
, Roberta Ghidoni
27
, Ole A Andreassen
41
147
148
, Peter A Holmans
134
, Pascual Sánchez-Juan
17
149
, Rebecca Sims
134
, Nancy Y Ip
13
14
51
52
, Kun Ho Lee
9
11
12
150
, Takeshi Ikeuchi
8
, Alfredo Ramirez
67
68
117
131
151
, Agustin Ruiz
6
17
152
, Mikko Hiltunen
5
, Jean-Charles Lambert
4
, Cornelia van Duijn
3
153
, Mike Nalls
2
, Ruth Frikke-Schmidt
1
154
Affiliations
Affiliations
- 1 Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
- 2 Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD, USA.
- 3 Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- 4 Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
- 5 Institute of Biomedicine, University of Eastern Finland, Yliopistoranta 1E, 70211 Kuopio, Finland.
- 6 Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.
- 7 UK Dementia Research Institute, School of Medicine, Cardiff University, Wales, UK.
- 8 Department of Molecular Genetics, Brain Research Institute, Niigata University, Japan.
- 9 Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea.
- 10 Well-aging Medicare Institute & CSU G-LAMP Project Group, Chosun University, Gwangju, 61452, Republic of Korea.
- 11 BK FOUR Department of Integrative Biological Sciences, Chosun University, Gwangju, 61452, Republic of Korea.
- 12 Gwangju Alzheimer's & Related Dementia (GARD) Cohort Research Center, Chosun University, Gwangju, 61452, Republic of Korea.
- 13 Division of Life Science, State Key Laboratory of Molecular Neuroscience and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
- 14 Hong Kong Center for Neurodegenerative Diseases, InnoHK, Hong Kong, China.
- 15 VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
- 16 Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
- 17 Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
- 18 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- 19 Laboratorio de Genética. Hospital Universitario Central de Asturias, Oviedo, Spain.
- 20 Instituto de Investigación Sanitaria del Principado de Asturias (ISPA).
- 21 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
- 22 Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- 23 The Research Centre for Age-related Functional Decline and Disease, Innlandet Hospital Trust, Ottestad, Norway.
- 24 Norwegian National Centre for Aging and Health, Vestfold Health Trust, Tønsberg, Norway.
- 25 Coalition for Aligning Science, 5425 Wisconsin Ave #600, Chevy Chase, MD 20815, USA.
- 26 Department of Clinical and Experimental Sciences, University of Brescia, Italy.
- 27 Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- 28 Laboratory of Experimental Neuropsychobiology, Clinical Neuroscience and Neurorehabilitation Department, IRCCS Santa Lucia Foundation, Rome, Italy.
- 29 Centro de Biología Molecular Severo Ochoa (UAM-CSIC).
- 30 Instituto de Investigacion Sanitaria 'Hospital la Paz' (IdIPaz), Madrid, Spain.
- 31 Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
- 32 Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
- 33 Grupo de Medicina Xenómica, CIBERER, CIMUS. Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
- 34 Fundación Pública Galega de Medicina Xenómica- IDIS, Santiago de Compostela, Spain.
- 35 Faculty of Medicine, University of Lisbon, Portugal.
- 36 Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Germany.
- 37 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
- 38 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
- 39 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
- 40 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
- 41 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 42 Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 43 University of Bordeaux, Inserm Bordeaux Population Health Research Center U1219, Bordeaux, France.
- 44 German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
- 45 Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
- 46 UKDRI@ Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
- 47 Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
- 48 Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- 49 Karolinska University Hospital, Theme inflammation and Aging, Sweden.
- 50 Karolinska Institutet, Center for Alzheimer Research, Department NVS, Division of ARC, Stockholm, Sweden.
- 51 Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, 518057, China.
- 52 SIAT-HKUST Joint Laboratory for Brain Science, Shenzhen, Guangdong, 518055, China.
- 53 Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.
- 54 Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
- 55 Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
- 56 Hospital Universitario Ramon y Cajal, IRYCIS, Madrid.
- 57 Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany.
- 58 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
- 59 Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland.
- 60 Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
- 61 Université Paris Cité, EA 4468, APHP, Hospital Broca, Memory Resource and Research Centre of de Paris-Broca-Ile de France, Paris, France.
- 62 Department of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Germany.
- 63 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
- 64 Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Czech Republic.
- 65 International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.
- 66 Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- 67 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
- 68 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
- 69 Center for Noninvasive Diagnostics, TGen, Phoenix, AZ, USA.
- 70 Department of Neurosurgery, Kuopio University Hospital, Puijonlaaksontie 2 FI-70210 Kuopio, Finland.
- 71 Institute of Clinical Medicine-Neurosurgery, University of Eastern Finland, Kuopio, Finland.
- 72 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen.
- 73 Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.
- 74 Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Italy.
- 75 Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
- 76 Clinic of Neurology, UH "Alexandrovska", Medical University - Sofia, Sofia, Bulgaria.
- 77 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
- 78 Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain.
- 79 Institute for Urban Public Health, University Hospital of University Duisburg-Essen, Essen, Germany.
- 80 Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, U.K.
- 81 Neurological Tissue Bank - Biobanc- Hospital Clinic -IDIBAPS, Barcelona, Spain.
- 82 Alzheimer's disease and other cognitive disorders Unit. Neurology Department, Hospital Clinic, Barcelona, Spain.
- 83 Department of Neurology. Hospital Universitario Donostia. San Sebastian, Spain.
- 84 Neurosciences Area. Instituto Biodonostia. San Sebastian, Spain.
- 85 Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence, Florence, Italy.
- 86 IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
- 87 Centre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy.
- 88 Fundació Docència i Recerca MútuaTerrassa, Terrassa, Barcelona, Spain.
- 89 Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain.
- 90 Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Valencia, Spain.
- 91 German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
- 92 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Hindenburgdamm 30, 12203 Berlin, Germany.
- 93 Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 94 Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
- 95 Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.
- 96 Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain.
- 97 Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
- 98 Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland.
- 99 Institute for Regenerative Medicine, University of Zürich, Switzerland.
- 100 Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy.
- 101 Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain.
- 102 Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología. Facultad de Medicina. Universidad de Málaga. Málaga, Spain.
- 103 Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103 Leipzig, Germany.
- 104 Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria and IDIVAL), Santander, Spain.
- 105 Haugesund Hospital, Department of Research and Innovation, Haugesund, Norway.
- 106 Unit of Neurology V - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
- 107 Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
- 108 Martin-Luther-University Halle-Wittenberg, University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Halle (Saale), Germany.
- 109 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Department of Geriatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
- 110 CAEBI, Centro Andaluz de Estudios Bioinformáticos, Sevilla, Spain.
- 111 Alzheimer's disease and other cognitive disorders unit. Service of Neurology. Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
- 112 Department of Immunology, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Las Palmas, Spain.
- 113 Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Depatment of Neurology, Columbia University, New York, NY.
- 114 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
- 115 Department of Neurology and Clinical Neurophysiology, Trondheim University Hospital, Trondheim, Norway.
- 116 Department of Psychiatry and Psychotherapy, LVR-Klinikum Essen, University of Duisburg-Essen, Germany.
- 117 Department for Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Bonn, Germany.
- 118 Norwegian National Advisory Unit on Aging and Health, Vestfold Health Trust, Tønsberg, Norway.
- 119 Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
- 120 Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway.
- 121 Department of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy.
- 122 Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, University of Bari "A. Moro, Bari, Italy.
- 123 Academic Division "C. Frugoni" & Hospital Division of Internal and Geriatric Medicine, Policlinico Hospital, Bari, Italy.
- 124 Department of Medicine and Surgery, Unit of Neurology, University-Hospital of Parma, Parma, Italy.
- 125 Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
- 126 Namsos Hospital, Namsos, Norway.
- 127 Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 128 Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
- 129 Neurology Unit, IRCCS "San Gerardo dei Tintori", Monza, Italy.
- 130 School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
- 131 Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- 132 Estudios en Neurociencias y Sistemas Complejos (ENyS) CONICET-HEC-UNAJ.
- 133 Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 134 Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Wales, UK.
- 135 Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
- 136 German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
- 137 Medical Science Department, iBiMED, Aveiro, Portugal.
- 138 Department of Old Age Psychiatry, Division of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
- 139 Wolfson Centre for Age Related Diseases, Division of Neuroscience of the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
- 140 Stavanger University Hospital, Stavanger, Norway.
- 141 Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France.
- 142 VIB Center for Brain and Disease Research, ON5 Herestraat 49 - box 602, 3000 Leuven, Belgium.
- 143 Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
- 144 Bristol Medical School, University of Bristol, Bristol, UK.
- 145 Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
- 146 Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
- 147 Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
- 148 KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway.
- 149 Alzheimer's Centre Reina Sofia-CIEN Foundation, Madrid, Spain.
- 150 Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, 41062, Repuiblic of Korea.
- 151 Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.
- 152 Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA.
- 153 Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
- 154 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2100 Copenhagen, Denmark.
- PMID: 40385391
- PMCID: PMC12083631
- DOI: 10.1101/2025.05.07.25327065
Item in Clipboard
APOE stratified genome-wide association studies provide novel insights into the genetic etiology of Alzheimers's disease
Jesper Qvist Thomassen et al.
medRxiv.
.
Display options
Format
[Preprint]. 2025 May 9:2025.05.07.25327065.
doi: 10.1101/2025.05.07.25327065.
Authors
Jesper Qvist Thomassen
1
, Leonard Hampton
2
, Brittany Ulms
3
, Benjamin Grenier-Boley
4
, Sami Heikkinen
5
, Pablo Garcia
6
, Atahualapa Castillo-Morales
7
, Masataka Kikuchi
8
, Jungsoo Gim
9
10
11
12
, Han Cao
13
14
, Fahri Küçükali
15
16
, Najaf Amin
3
, Dabin Yoon
9
10
, Itziar de Rojas
6
17
18
, Pilar Alvarez Jerez
2
, Victoria Alvarez
19
20
, Beatrice Arosio
21
22
, Celine Bellenguez
4
, Sverre Bergh
23
24
, Kimberly Billingsley
2
, Cornelis Blauwendraat
25
, Merce Boada
6
17
, Barbara Borroni
26
27
, Paola Bossù
28
, María J Bullido
17
29
30
, Antonio Daniele
31
32
, Ángel Carracedo
33
34
, Alexandre de Mendonça
35
, Mark Cookson
2
, Jürgen Deckert
36
, Martin Dichgans
37
38
39
, Srdjan Djurovic
40
41
, Oriol Dols-Icardo
17
42
, Carole Dufouil
43
, Emrah Düzel
44
45
, Valentina Escott-Price
46
, Tormod Fladby
47
48
, Laura Fratiglioni
49
50
, Amy K Y Fu
13
14
51
52
, Daniela Galimberti
53
54
, Jose Maria García-Alberca
2
17
, Vilmantas Giedraitis
55
, Guillermo Garcia-Ribas
56
, Caroline Graff
49
50
, Timo Grimmer
57
, Edna Grünblatt
58
59
60
, OIivier Hanon
61
, Lucrezia Hausner
62
, Stefanie Heilmann-Hemibach
63
, Jakub Hort
64
65
, Frank Jessen
66
67
68
, Kendall Jensen
69
, Caroline Jonson
2
, Yoontae Kim
10
11
, Nicole Kuznetsov
2
, Ville Leinonen
70
71
, Anssi Lipponen
5
, Jiao Luo
1
72
, Mary Makarious
2
, Henna Martiskainen
5
, Carlo Masullo
73
, Patrizia Mecocci
74
75
, Shima Mehrabian
76
, Pablo Mir
17
77
78
, Akinori Miyashita
8
, Susanne Moebus
79
, Kin Y Mok
13
14
80
, Laura Molina Porcel
81
82
, Fermin Moreno
17
83
84
, Benedetta Nacmias
85
86
, Lucilla Parnetti
87
, Pau Pastor
88
89
, Jordi Pérez-Tur
17
90
, Oliver Peters
91
92
, Yolande A L Pijnenburg
93
94
, Gerard Piñol-Ripoll
95
96
, Julius Popp
97
98
99
, Innocenzo Rainero
100
, Luis M Real
101
102
, Steffi Riedel-Heller
103
, Eloy Rodriguez-Rodriguez
17
104
, Arvid Rongve
105
, Giacomina Rossi
106
, Jose Luis Royo
102
, Dan Rujescu
107
108
, Ingvild Saltvedt
109
, María Eugenia Sáez
110
, Raquel Sánchez-Valle
111
, Florentino Sanchez-Garcia
112
, Nicolai Sandau
1
, Nikolaos Scarmeas
113
114
, Katja Scheffler
109
115
, Norbert Scherbaum
116
, Anja Schneider
67
117
, Geir Selbæk
118
119
120
, Davide Seripa
121
, Vincenzo Solfrizzi
122
123
, Marco Spallazzi
124
, Alessio Squassina
125
, Eystein Stordal
126
, Niccoló Tesi
94
127
128
, Lucio Tremolizzo
129
130
, Kumar P Tripathi
131
132
, Wiesje M van der Flier
93
94
133
, Julie Williams
7
134
, Jens Wiltfang
135
136
137
, Dag Aarsland
138
139
140
, Andrew B Singleton
2
, Philippe Amouyel
4
, Stéphanie Debette
43
, Gael Nicolas
141
, Sven van der Lee
93
94
127
, Henne Holstege
93
94
127
142
143
, Maria Victoria Fernandez
6
, Patrick Gavin Kehoe
144
, Kristel Sleegers
15
16
, Martin Ingelsson
55
145
146
, Roberta Ghidoni
27
, Ole A Andreassen
41
147
148
, Peter A Holmans
134
, Pascual Sánchez-Juan
17
149
, Rebecca Sims
134
, Nancy Y Ip
13
14
51
52
, Kun Ho Lee
9
11
12
150
, Takeshi Ikeuchi
8
, Alfredo Ramirez
67
68
117
131
151
, Agustin Ruiz
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, Mikko Hiltunen
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, Jean-Charles Lambert
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, Cornelia van Duijn
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, Mike Nalls
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, Ruth Frikke-Schmidt
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Affiliations
- 1 Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark.
- 2 Center for Alzheimer's and Related Dementias, National Institute on Aging, Bethesda, MD, USA.
- 3 Nuffield Department of Population Health, University of Oxford, Oxford, UK.
- 4 Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
- 5 Institute of Biomedicine, University of Eastern Finland, Yliopistoranta 1E, 70211 Kuopio, Finland.
- 6 Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya (UIC), Barcelona, Spain.
- 7 UK Dementia Research Institute, School of Medicine, Cardiff University, Wales, UK.
- 8 Department of Molecular Genetics, Brain Research Institute, Niigata University, Japan.
- 9 Department of Biomedical Science, Chosun University, Gwangju, 61452, Republic of Korea.
- 10 Well-aging Medicare Institute & CSU G-LAMP Project Group, Chosun University, Gwangju, 61452, Republic of Korea.
- 11 BK FOUR Department of Integrative Biological Sciences, Chosun University, Gwangju, 61452, Republic of Korea.
- 12 Gwangju Alzheimer's & Related Dementia (GARD) Cohort Research Center, Chosun University, Gwangju, 61452, Republic of Korea.
- 13 Division of Life Science, State Key Laboratory of Molecular Neuroscience and Daniel and Mayce Yu Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.
- 14 Hong Kong Center for Neurodegenerative Diseases, InnoHK, Hong Kong, China.
- 15 VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
- 16 Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
- 17 Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid, Spain.
- 18 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- 19 Laboratorio de Genética. Hospital Universitario Central de Asturias, Oviedo, Spain.
- 20 Instituto de Investigación Sanitaria del Principado de Asturias (ISPA).
- 21 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
- 22 Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- 23 The Research Centre for Age-related Functional Decline and Disease, Innlandet Hospital Trust, Ottestad, Norway.
- 24 Norwegian National Centre for Aging and Health, Vestfold Health Trust, Tønsberg, Norway.
- 25 Coalition for Aligning Science, 5425 Wisconsin Ave #600, Chevy Chase, MD 20815, USA.
- 26 Department of Clinical and Experimental Sciences, University of Brescia, Italy.
- 27 Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- 28 Laboratory of Experimental Neuropsychobiology, Clinical Neuroscience and Neurorehabilitation Department, IRCCS Santa Lucia Foundation, Rome, Italy.
- 29 Centro de Biología Molecular Severo Ochoa (UAM-CSIC).
- 30 Instituto de Investigacion Sanitaria 'Hospital la Paz' (IdIPaz), Madrid, Spain.
- 31 Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.
- 32 Neurology Unit, IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy.
- 33 Grupo de Medicina Xenómica, CIBERER, CIMUS. Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
- 34 Fundación Pública Galega de Medicina Xenómica- IDIS, Santiago de Compostela, Spain.
- 35 Faculty of Medicine, University of Lisbon, Portugal.
- 36 Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Germany.
- 37 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
- 38 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
- 39 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
- 40 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
- 41 Centre for Precision Psychiatry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
- 42 Department of Neurology, Institut de Recerca Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 43 University of Bordeaux, Inserm Bordeaux Population Health Research Center U1219, Bordeaux, France.
- 44 German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
- 45 Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany.
- 46 UKDRI@ Cardiff, School of Medicine, Cardiff University, Cardiff, UK.
- 47 Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
- 48 Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
- 49 Karolinska University Hospital, Theme inflammation and Aging, Sweden.
- 50 Karolinska Institutet, Center for Alzheimer Research, Department NVS, Division of ARC, Stockholm, Sweden.
- 51 Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, 518057, China.
- 52 SIAT-HKUST Joint Laboratory for Brain Science, Shenzhen, Guangdong, 518055, China.
- 53 Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda, Ospedale Policlinico, Milan, Italy.
- 54 Dept. of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
- 55 Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Uppsala, Sweden.
- 56 Hospital Universitario Ramon y Cajal, IRYCIS, Madrid.
- 57 Center for Cognitive Disorders, Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany.
- 58 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
- 59 Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland.
- 60 Zurich Center for Integrative Human Physiology, University of Zurich, Switzerland.
- 61 Université Paris Cité, EA 4468, APHP, Hospital Broca, Memory Resource and Research Centre of de Paris-Broca-Ile de France, Paris, France.
- 62 Department of Geriatric Psychiatry, Central Institute for Mental Health Mannheim, Faculty Mannheim, University of Heidelberg, Germany.
- 63 Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
- 64 Memory Clinic, Department of Neurology, Charles University, Second Faculty of Medicine and Motol University Hospital, Czech Republic.
- 65 International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic.
- 66 Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- 67 German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
- 68 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
- 69 Center for Noninvasive Diagnostics, TGen, Phoenix, AZ, USA.
- 70 Department of Neurosurgery, Kuopio University Hospital, Puijonlaaksontie 2 FI-70210 Kuopio, Finland.
- 71 Institute of Clinical Medicine-Neurosurgery, University of Eastern Finland, Kuopio, Finland.
- 72 Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen.
- 73 Institute of Neurology, Catholic University of the Sacred Heart, Rome, Italy.
- 74 Division of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Italy.
- 75 Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
- 76 Clinic of Neurology, UH "Alexandrovska", Medical University - Sofia, Sofia, Bulgaria.
- 77 Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
- 78 Departamento de Medicina, Facultad de Medicina, Universidad de Sevilla, Seville, Spain.
- 79 Institute for Urban Public Health, University Hospital of University Duisburg-Essen, Essen, Germany.
- 80 Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, U.K.
- 81 Neurological Tissue Bank - Biobanc- Hospital Clinic -IDIBAPS, Barcelona, Spain.
- 82 Alzheimer's disease and other cognitive disorders Unit. Neurology Department, Hospital Clinic, Barcelona, Spain.
- 83 Department of Neurology. Hospital Universitario Donostia. San Sebastian, Spain.
- 84 Neurosciences Area. Instituto Biodonostia. San Sebastian, Spain.
- 85 Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence, Florence, Italy.
- 86 IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
- 87 Centre for Memory Disturbances, Lab of Clinical Neurochemistry, Section of Neurology, University of Perugia, Perugia, Italy.
- 88 Fundació Docència i Recerca MútuaTerrassa, Terrassa, Barcelona, Spain.
- 89 Memory Disorders Unit, Department of Neurology, Hospital Universitari Mutua de Terrassa, Terrassa, Barcelona, Spain.
- 90 Unitat de Genètica Molecular, Institut de Biomedicina de València-CSIC, Valencia, Spain.
- 91 German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
- 92 Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Psychiatry and Psychotherapy, Hindenburgdamm 30, 12203 Berlin, Germany.
- 93 Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 94 Amsterdam Neuroscience, Neurodegeneration, Amsterdam, The Netherlands.
- 95 Unitat Trastorns Cognitius, Hospital Universitari Santa Maria de Lleida, Lleida, Spain.
- 96 Institut de Recerca Biomedica de Lleida (IRBLLeida), Lleida, Spain.
- 97 Old Age Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
- 98 Department of Geriatric Psychiatry, University Hospital of Psychiatry Zürich, Zürich, Switzerland.
- 99 Institute for Regenerative Medicine, University of Zürich, Switzerland.
- 100 Department of Neuroscience "Rita Levi Montalcini", University of Torino, Torino, Italy.
- 101 Unidad Clínica de Enfermedades Infecciosas y Microbiología. Hospital Universitario de Valme, Sevilla, Spain.
- 102 Depatamento de Especialidades Quirúrgicas, Bioquímica e Inmunología. Facultad de Medicina. Universidad de Málaga. Málaga, Spain.
- 103 Institute of Social Medicine, Occupational Health and Public Health, University of Leipzig, 04103 Leipzig, Germany.
- 104 Neurology Service, Marqués de Valdecilla University Hospital (University of Cantabria and IDIVAL), Santander, Spain.
- 105 Haugesund Hospital, Department of Research and Innovation, Haugesund, Norway.
- 106 Unit of Neurology V - Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
- 107 Department of Psychiatry and Psychotherapy, Medical University Vienna, Vienna, Austria.
- 108 Martin-Luther-University Halle-Wittenberg, University Clinic and Outpatient Clinic for Psychiatry, Psychotherapy and Psychosomatics, Halle (Saale), Germany.
- 109 Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Department of Geriatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
- 110 CAEBI, Centro Andaluz de Estudios Bioinformáticos, Sevilla, Spain.
- 111 Alzheimer's disease and other cognitive disorders unit. Service of Neurology. Hospital Clínic of Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
- 112 Department of Immunology, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Las Palmas, Spain.
- 113 Taub Institute for Research in Alzheimer's Disease and the Aging Brain, The Gertrude H. Sergievsky Center, Depatment of Neurology, Columbia University, New York, NY.
- 114 1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens, Medical School, Greece.
- 115 Department of Neurology and Clinical Neurophysiology, Trondheim University Hospital, Trondheim, Norway.
- 116 Department of Psychiatry and Psychotherapy, LVR-Klinikum Essen, University of Duisburg-Essen, Germany.
- 117 Department for Cognitive Disorders and Old Age Psychiatry, University Hospital Bonn, Bonn, Germany.
- 118 Norwegian National Advisory Unit on Aging and Health, Vestfold Health Trust, Tønsberg, Norway.
- 119 Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway.
- 120 Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway.
- 121 Department of Hematology and Stem Cell Transplant, Vito Fazzi Hospital, Lecce, Italy.
- 122 Interdisciplinary Department of Medicine, Geriatric Medicine and Memory Unit, University of Bari "A. Moro, Bari, Italy.
- 123 Academic Division "C. Frugoni" & Hospital Division of Internal and Geriatric Medicine, Policlinico Hospital, Bari, Italy.
- 124 Department of Medicine and Surgery, Unit of Neurology, University-Hospital of Parma, Parma, Italy.
- 125 Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
- 126 Namsos Hospital, Namsos, Norway.
- 127 Genomics of Neurodegenerative Diseases and Aging, Human Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 128 Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands.
- 129 Neurology Unit, IRCCS "San Gerardo dei Tintori", Monza, Italy.
- 130 School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
- 131 Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
- 132 Estudios en Neurociencias y Sistemas Complejos (ENyS) CONICET-HEC-UNAJ.
- 133 Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
- 134 Division of Psychological Medicine and Clinical Neuroscience, School of Medicine, Cardiff University, Wales, UK.
- 135 Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, Goettingen, Germany.
- 136 German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany.
- 137 Medical Science Department, iBiMED, Aveiro, Portugal.
- 138 Department of Old Age Psychiatry, Division of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
- 139 Wolfson Centre for Age Related Diseases, Division of Neuroscience of the Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.
- 140 Stavanger University Hospital, Stavanger, Norway.
- 141 Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and Reference Center for Developmental Disorders, Rouen, France.
- 142 VIB Center for Brain and Disease Research, ON5 Herestraat 49 - box 602, 3000 Leuven, Belgium.
- 143 Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
- 144 Bristol Medical School, University of Bristol, Bristol, UK.
- 145 Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada.
- 146 Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada.
- 147 Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
- 148 KG Jebsen Centre for Neurodevelopmental disorders, University of Oslo, Oslo, Norway.
- 149 Alzheimer's Centre Reina Sofia-CIEN Foundation, Madrid, Spain.
- 150 Department of Neural Development and Disease, Korea Brain Research Institute, Daegu, 41062, Repuiblic of Korea.
- 151 Department of Psychiatry & Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, San Antonio, TX, USA.
- 152 Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center, San Antonio, Texas, USA.
- 153 Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
- 154 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2100 Copenhagen, Denmark.
- PMID: 40385391
- PMCID: PMC12083631
- DOI: 10.1101/2025.05.07.25327065
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Abstract
Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E gene (APOE) ε2/ε3/ε4 polymorphism remains the longstanding benchmark for genetic disease risk with a consistently large effect across studies1-10. Despite this massive signal, the exact mechanisms for how ε4 increases and for how ε2 decreases dementia risk is not well-understood. Importantly, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in s4 carriers11-13, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. Such insights may help to understand and overcome side effects, to impact clinical trial enrolment strategies, and to create the scientific basis for targeted mechanism-driven therapies in neurodegenerative diseases.
Figures
Figure 1:. Flow chart of study
Flow…
Figure 1:. Flow chart of study
Flow chart illustrating the included multi-ancestry cohorts and analysis…
Flow chart illustrating the included multi-ancestry cohorts and analysis strategies.
Figure 2:. Miami plot of the APOE …
Figure 2:. Miami plot of the APOE ε33 and ε44+ε43 strata.
The Manhattan plot for…
The Manhattan plot for the APOE ε44+ε43 strata is shown in blue in the upper part of the figure and for the APOE ε33 strata in orange in the lower part of the figure. Genome wide significant loci are annotated with the nearest gene (known loci in black and new in red). Two-sided raw P-values were derived from a fixed-effect meta-analysis. The red dashed lines show the genome-wide significant level (P=5×10−8). APOE: Apolipoprotein E gene.
Figure 3:. Loci and forest plots for …
Figure 3:. Loci and forest plots for SLC50A1, TMEM106B, NPAS3 , and SHARPIN where the…
Loci plots for SLC50A1 (A), TMEM106B (B), NPAS3 (C), SHARPIN (D) in APOE ε33 and APOE ε44+ε43 strata. Forest plots for the lead SNPs in the four APOE strata ε33, ε44+ε43, ε43 and ε44. In the forest plot each APOE strata is shown to visualize potential dominant or additive interaction.
Figure 4:. Loci and forest plots for…
Figure 4:. Loci and forest plots for the three loci ( HLA-DRA -1, CLU, DDHD1 …
Loci plots for HLA-DRA -1 (A), CLU (B), DDHD1 (C) in APOE ε33 and APOE ε44+ε43 strata. Forest plots for the lead SNPs in the four APOE strata ε33, ε44+ε43, ε43 and ε44. In the forest plot each APOE strata is shown to visualize potential dominant or additive interaction.
Figure 5:. Multi-ancestry evaluation
A: Multi-ancestry results…
Figure 5:. Multi-ancestry evaluation
A: Multi-ancestry results for lead variant in HLA-DRA locus. B: Multi-ancestry…
A: Multi-ancestry results for lead variant in HLA-DRA locus. B: Multi-ancestry results for lead variant in DDHD1 locus. AAC: Asian American, AFR: African American, AMR: Admixed American, CHN: Hong-Kong Chinese, JPN: Japanese, KOR: Korean, EAS: East Asian ancestry meta-analysis, EUR: European ancestry meta-analysis.
Figure 6:. Variant and gene-based significant loci
Figure 6:. Variant and gene-based significant loci
Venn-diagram of the genome-wide significant loci associated with…
Venn-diagram of the genome-wide significant loci associated with AD, showing the overlap between APOE-strata and between variant based testing (main GWAS) and gene-based testing (MAGMA).
References
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- de Rojas I. et al. Common variants in Alzheimer’s disease: Novel association of six genetic variants with AD and risk stratification by polygenic risk scores. medRxiv (2020).
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