Predicting cognitive decline: Which is more useful, baseline amyloid levels or longitudinal change?
(2024) NeuroImage: Clinical, 41, art. no. 103551, .
Chen, G.a b , McKay, N.S.a b , Gordon, B.A.a b c , Liu, J.d , Joseph-Mathurin, N.a b , Schindler, S.E.e , Hassenstab, J.e , Aschenbrenner, A.J.b e , Wang, Q.a b , Schultz, S.A.h , Su, Y.i , LaMontagne, P.J.a b , Keefe, S.J.a b , Massoumzadeh, P.a b , Cruchaga, C.f , Xiong, C.g , Morris, J.C.a b c , Benzinger, T.L.S.a b c
a Departments of Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
b Knight Alzheimer’s Disease Research Center, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
d Department of Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
e Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
f Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
g Divison of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO, United States
h Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
i Banner Alzheimer’s Institute, Phoenix, AZ, United States
Abstract
The use of biomarkers for the early detection of Alzheimer’s disease (AD) is crucial for developing potential therapeutic treatments. Positron Emission Tomography (PET) is a well-established tool used to detect β-amyloid (Aβ) plaques in the brain. Previous studies have shown that cross-sectional biomarkers can predict cognitive decline (Schindler et al.,2021). However, it is still unclear whether longitudinal Aβ-PET may have additional value for predicting time to cognitive impairment in AD. The current study aims to evaluate the ability of baseline- versus longitudinal rate of change in-11C-Pittsburgh compound B (PiB) Aβ-PET to predict cognitive decline. A cohort of 153 participants who previously underwent PiB-PET scans and comprehensive clinical assessments were used in this study. Our analyses revealed that baseline Aβ is significantly associated with the rate of change in cognitive composite scores, with cognition declining more rapidly when baseline PiB Aβ levels were higher. In contrast, no signification association was identified between the rate of change in PiB-PET Aβ and cognitive decline. Additionally, the ability of the rate of change in the PiB-PET measures to predict cognitive decline was significantly influenced by APOE ε4 carrier status. These results suggest that a single PiB-PET scan is sufficient to predict cognitive decline and that longitudinal measures of Aβ accumulation do not improve the prediction of cognitive decline once someone is amyloid positive. © 2023 The Authors
Author Keywords
Alzheimer’s disease; Amyloid; Cognition; Longitudinal study; PET
Funding details
National Institutes of HealthNIHNCRR 1S10RR022984-01A1, P01AG003991, P01AG026276, P30NS09857781, P50AG00561, R01AG043434, R01EB009352, UL1TR000448, UL1TR002345
Document Type: Article
Publication Stage: Final
Source: Scopus
Diffusion basis spectrum imaging detects subclinical traumatic optic neuropathy in a closed-head impact mouse model of traumatic brain injury
(2023) Frontiers in Neurology, 14, art. no. 1269817, .
Yang, H.-C.a f g , Lavadi, R.S.a , Sauerbeck, A.D.b c , Wallendorf, M.d , Kummer, T.T.b c e , Song, S.-K.a c , Lin, T.-H.a f g
a Department of Radiology, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
c Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
d Department of Biostatistics, Washington University School of Medicine, St. Louis, MO, United States
e VA Medical Center, St. Louis, MO, United States
f Chemistry, Washington University in St. Louis, St. Louis, MO, United States
g Bioimaging, GSK, Collegeville, PA, United States
Abstract
Introduction: Traumatic optic neuropathy (TON) is the optic nerve injury secondary to brain trauma leading to visual impairment and vision loss. Current clinical visual function assessments often fail to detect TON due to slow disease progression and clinically silent lesions resulting in potentially delayed or missed treatment in patients with traumatic brain injury (TBI). Methods: Diffusion basis spectrum imaging (DBSI) is a novel imaging modality that can potentially fill this diagnostic gap. Twenty-two, 16-week-old, male mice were equally divided into a sham or TBI (induced by moderate Closed-Head Impact Model of Engineered Rotational Acceleration device) group. Briefly, mice were anesthetized with isoflurane (5% for 2.5 min followed by 2.5% maintenance during injury induction), had a helmet placed over the head, and were placed in a holder prior to a 2.1-joule impact. Serial visual acuity (VA) assessments, using the Virtual Optometry System, and DBSI scans were performed in both groups of mice. Immunohistochemistry (IHC) and histological analysis of optic nerves was also performed after in vivo MRI. Results: VA of the TBI mice showed unilateral or bilateral impairment. DBSI of the optic nerves exhibited bilateral involvement. IHC results of the optic nerves revealed axonal loss, myelin injury, axonal injury, and increased cellularity in the optic nerves of the TBI mice. Increased DBSI axon volume, decreased DBSI λ||, and elevated DBSI restricted fraction correlated with decreased SMI-312, decreased SMI-31, and increased DAPI density, respectively, suggesting that DBSI can detect coexisting pathologies in the optic nerves of TBI mice. Conclusion: DBSI provides an imaging modality capable of detecting subclinical changes of indirect TON in TBI mice. Copyright © 2023 Yang, Lavadi, Sauerbeck, Wallendorf, Kummer, Song and Lin.
Author Keywords
axonal loss; diffusion basis spectrum imaging; diffusion MRI; inflammation; modCHIMERA; traumatic brain injury; traumatic optic neuropathy
Funding details
National Institutes of HealthNIHR01-NS047592, R01-NS116091, R01-NS121612, U01-EY025500
U.S. Department of Veterans AffairsVA1I01BX005204-01
National Multiple Sclerosis SocietyNMSSRG 4549A4/1
Document Type: Article
Publication Stage: Final
Source: Scopus
Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease
(2023) Nature Genetics, .
Kim, J.J.a b , Vitale, D.a c d , Otani, D.V.e f , Lian, M.M.g h , Heilbron, K.i , Aslibekyan, S.i , Auton, A.i , Babalola, E.i , Bell, R.K.i , Bielenberg, J.i , Bryc, K.i , Bullis, E.i , Cannon, P.i , Coker, D.i , Partida, G.C.i , Dhamija, D.i , Das, S.i , Elson, S.L.i , Eriksson, N.i , Filshtein, T.i , Fitch, A.i , Fletez-Brant, K.i , Fontanillas, P.i , Freyman, W.i , Granka, J.M.i , Hernandez, A.i , Hicks, B.i , Hinds, D.A.i , Jewett, E.M.i , Jiang, Y.i , Kukar, K.i , Kwong, A.i , Lin, K.-H.i , Llamas, B.A.i , Lowe, M.i , McCreight, J.C.i , McIntyre, M.H.i , Micheletti, S.J.i , Moreno, M.E.i , Nandakumar, P.i , Nguyen, D.T.i , Noblin, E.S.i , O’Connell, J.i , Petrakovitz, A.A.i , Poznik, G.D.i , Reynoso, A.i , Schloetter, M.i , Schumacher, M.i , Shastri, A.J.i , Shelton, J.F.i , Shi, J.i , Shringarpure, S.i , Su, Q.J.i , Tat, S.A.i , Tchakouté, C.T.i , Tran, V.i , Tung, J.Y.i , Wang, X.i , Wang, W.i , Weldon, C.H.i , Wilton, P.i , Wong, C.D.i , Iwaki, H.a c d , Lake, J.a , Solsberg, C.W.j k l , Leonard, H.a c d , Makarious, M.B.a m n , Tan, E.-K.o , Singleton, A.B.a d , Bandres-Ciga, S.a d , Noyce, A.J.b , Gatto, E.M.q , Kauffman, M.r , Khachatryan, S.s , Tavadyan, Z.s , Shepherd, C.E.t , Hunter, J.u , Kumar, K.v , Ellis, M.w , Rentería, M.E.x , Koks, S.y , Zimprich, A.z , Schumacher-Schuh, A.F.aa , Rieder, C.ab , Awad, P.S.ac , Tumas, V.ad , Camargos, S.ae , Fon, E.A.af , Monchi, O.ag , Fon, T.ah , Galleguillos, B.P.ai , Miranda, M.aj , Bustamante, M.L.ak , Olguin, P.ai , Chana, P.al , Tang, B.am , Shang, H.an , Guo, J.ao , Chan, P.ap , Luo, W.aq , Arboleda, G.ar , Orozc, J.as , del Rio, M.J.at , Hernandez, A.au , Salama, M.av , Kamel, W.A.aw , Zewde, Y.Z.ax , Brice, A.ay , Corvol, J.-C.az , Westenberger, A.ba , Illarionova, A.bb , Mollenhauer, B.bc , Klein, C.ba , Vollstedt, E.-J.ba , Hopfner, F.bd , Höglinger, G.bd , Madoev, H.ba , Trinh, J.ba , Junker, J.ba , Lohmann, K.ba , Lange, L.M.ba be , Sharma, M.bf , Groppa, S.bg , Gasser, T.bf , Fang, Z.-H.bh , Akpalu, A.bi , Xiromerisiou, G.bj , Hadjigorgiou, G.bj , Dagklis, I.bk , Tarnanas, I.bl , Stefanis, L.bm , Stamelou, M.bn , Dadiotis, E.bj , Medina, A.bo , Chan, G.H.-F.bp , Ip, N.bq , Cheung, N.Y.-F.bp , Chan, P.bq , Zhou, X.bq , Kishore, A.br , Divya, K.P.bs , Pal, P.bt , Kukkle, P.L.bu , Rajan, R.bv , Borgohain, R.bw , Salari, M.bx , Quattrone, A.by , Valente, E.M.bz , Parnetti, L.ca , Avenali, M.bz , Schirinzi, T.cb , Funayama, M.cc , Hattori, N.cd , Shiraishi, T.ce , Karimova, A.cf , Kaishibayeva, G.cf , Shambetova, C.cg , Krüger, R.ch , Tan, A.H.ci , Ahmad-Annuar, A.ci , Norlinah, M.I.cj , Murad, N.A.A.ck , Azmin, S.cl , Lim, S.-Y.ci , Mohamed, W.cm , Tay, Y.W.ci , Martinez-Ramirez, D.cn , Rodriguez-Violante, M.co , Reyes-Pérez, P.cp , Tserensodnom, B.cq , Ojha, R.cr , Anderson, T.J.cs , Pitcher, T.L.cs , Sanyaolu, A.ct , Okubadejo, N.ct , Ojo, O.cu , Aasly, J.O.cv , Pihlstrøm, L.cw , Tan, M.cw , Ur-Rehman, S.cx , Veliz-Otani, D.e f , Cornejo-Olivas, M.cy , Doquenia, M.L.cz , Rosales, R.cz , Vinuela, A.da , Iakovenko, E.db , Mubarak, B.A.dc , Umair, M.dd , Amod, F.de , Carr, J.df , Bardien, S.df , Jeon, B.dg , Kim, Y.J.dh , Cubo, E.di , Alvarez, I.dj , Hoenicka, J.dk , Beyer, K.dl , Periñan, M.T.dm , Pastor, P.dn , El-Sadig, S.do , Brolin, K.dp , Zweier, C.dq , Tinkhauser, G.dr , Krack, P.dq , Lin, C.-H.ds , Wu, H.-C.dt , Kung, P.-J.du , Wu, R.-M.ds , Wu, Y.dt , Amouri, R.dv , Sassi, S.B.dw , Başak, A.N.dx , Genc, G.dy , Çakmak, Ö.Ö.dx , Ertan, S.dx , Martínez-Carrasco, A.m , Schrag, A.m , Schapira, A.m , Carroll, C.dz , Bale, C.ea , Grosset, D.eb , Stafford, E.J.m , Houlden, H.m , Morris, H.R.m n , Hardy, J.m , Mok, K.Y.m , Rizig, M.m , Wood, N.m , Williams, N.ec , Okunoye, O.m , Lewis, P.A.ed , Kaiyrzhanov, R.m , Weil, R.m , Love, S.ee , Stott, S.ef , Jasaityte, S.m , Dey, S.b , Obese, V.m , Espay, A.eg , O’Grady, A.eh , Sobering, A.K.ei , Siddiqi, B.eh , Casey, B.eh , Fiske, B.eh , Jonas, C.ej , Cruchaga, C.ek , Pantazis, C.B.d , Comart, C.eh , Wegel, C.el , Hall, D.em , Hernandez, D.a , Shiamim, E.en , Riley, E.eo , Faghri, F.c d , Serrano, G.E.ep , Chen, H.eq , Mata, I.F.p , Sarmiento, I.J.K.er , Williamson, J.en , Jankovic, J.es , Shulman, J.es et , Solle, J.C.eh , Murphy, K.eh , Nuytemans, K.eu , Kieburtz, K.ev , Markopoulou, K.ew , Marek, K.ex , Levine, K.S.c d , Chahine, L.M.ey , Ibanez, L.ez , Screven, L.d , Ruffrage, L.fa , Shulman, L.fb , Marsili, L.eg , Kuhl, M.eh , Dean, M.fa , Koretsky, M.a d , Puckelwartz, M.J.er , Inca-Martinez, M.p , Louie, N.eh , Mencacci, N.E.er , Albin, R.fc , Alcalay, R.fd , Walker, R.fe , Chowdhury, S.eh , Dumanis, S.ff , Lubbe, S.er , Xie, T.fg , Foroud, T.fh , Beach, T.ep , Sherer, T.eh , Song, Y.c d , Nguyen, D.fi , Nguyen, T.fi , Atadzhanov, M.fj , Blauwendraat, C.a d , Nalls, M.A.a c d , Foo, J.N.g h , Mata, I.p
a Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, United States
b Preventive Neurology Unit, Centre for Prevention Diagnosis and Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom
c Data Tecnica International, Washington, DC, United States
d Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States
e Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru
f Institute for Genome Sciences, University of Maryland, Baltimore, MD, United States
g Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore
h Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore
i 23andMe, Inc., Sunnyvale, CA, United States
j Pharmaceutical Sciences and Pharmacogenomics, UCSF, San Francisco, CA, United States
k Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, United States
l Memory and Aging Center, UCSF, San Francisco, CA, United States
m Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom
n UCL Movement Disorders Centre, University College London, London, United Kingdom
o Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore
p Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, United States
q Sanatorio de la Trinidad Mitre- INEBA, Buenos Aires, Argentina
r Hospital JM Ramos Mejia, Buenos Aires, Argentina
s Somnus Neurology Clinic, Yerevan, Armenia
t Neuroscience Research Australia, Sydney, NSW, Australia
u ANZAC Research Institute, Concord, NSW, Australia
v Garvan Institute of Medical Research and Concord Repatriation General Hospital, Darlinghurst, NSW, Australia
w Concord Hospital, Concord, NSW, Australia
x QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
y Murdoch University, Perth, WA, Australia
z Medical University Vienna Austria, Vienna, Austria
aa Universidade Federal do Rio Grande do Sul / Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
ab Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
ac Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
ad University of São Paulo, São Paulo, Brazil
ae Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
af Montreal Neurological Institute, Montreal, Quebec, Canada
ag Institut universitaire de gériatrie de Montréal, Montreal, QC, Canada
ah McGill University, Montreal, Quebec, Canada
ai Universidad de Chile, Santiago, Chile
aj Fundación Diagnosis, Santiago, Chile
ak Faculty of Medicine Universidad de Chile, Santiago, Chile
al CETRAM, Santiago, Chile
am Central South University, Changsha, China
an West China Hospital Sichuan University, Chengdu, China
ao Xiangya Hospital, Changsha, China
ap Capital Medical University, Beijing, China
aq Zhejiang University, Hangzhou, China
ar Universidad Nacional de Colombia, Bogotá, Colombia
as Fundación Valle del Lili, Santiago De Cali, Colombia
at University of Antioquia, Medellin, Colombia
au University of Costa Rica, San Jose, Costa Rica
av The American University in Cairo, Cairo, Egypt
aw Beni-Suef University, Beni Suef, Egypt
ax Addis Ababa University, Addis Ababa, Ethiopia
ay Paris Brain Institute, Paris, France
az Sorbonne Université, Paris, France
ba University of Lübeck, Lübeck, Germany
bb Deutsches Zentrum für Neurodegenerative Erkrankungen, Göttingen, Germany
bc University Medical Center Göttingen, Göttingen, Germany
bd Department of Neurology, University Hospital, LMU Munich, Munich, Germany
be University Medical Center Schleswig-Holstein, Lübeck, Germany
bf University of Tubingen, Tübingen, Germany
bg University of Mainz, Mainz, Germany
bh The German Center for Neurodegenerative Diseases, Göttingen, Germany
bi University of Ghana Medical School, Accra, Ghana
bj University of Thessaly, Volos, Greece
bk Aristotle University of Thessaloniki, Thessaloniki, Greece
bl Ionian University, Corfu, Greece
bm Biomedical research Foundation of the Academy of Athens, Athens, Greece
bn Diagnostic and Therapeutic Centre HYGEIA Hospital, Marousi, Greece
bo Hospital San Felipe, Tegucigalpa, Honduras
bp Queen Elizabeth Hospital, Kowloon, Hong Kong
bq The Hong Kong University of Science and Technology, Kowloon, Hong Kong
br Aster Medcity, Kochi, India
bs Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India
bt National Institute of Mental Health & Neurosciences, Bengaluru, India
bu Manipal Hospital, Delhi, India
bv All India Institute of Medical Sciences, Delhi, India
bw Nizam’s Institute of Medical Sciences, Hyderabad, India
bx Shahid Beheshti University of Medical Science, Tehran, Iran
by Magna Græcia University of Catanzaro, Catanzaro, Italy
bz University of Pavia, Pavia, Italy
ca University of Perugia, Perugia, Italy
cb University of Rome Tor Vergata, Rome, Italy
cc Juntendo University, Tokyo, Japan
cd Faculty of Medicine, Juntendo University, Tokyo, Japan
ce Jikei University School of Medicine, Tokyo, Japan
cf Institute of Neurology and Neurorehabilitation, Almaty, Kazakhstan
cg Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan
ch University of Luxembourg, Luxembourg, Luxembourg
ci University of Malaya, Kuala Lumpur, Malaysia
cj Universiti Kebangsaan Malaysia, Selangor, Malaysia
ck UKM Medical Molecular Biology Institute, Kuala Lumpur, Malaysia
cl Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
cm International Islamic University, Kuala Lumpur, Malaysia
cn Tecnologico de Monterrey, Monterrey, Mexico
co Instituto Nacional de Neurologia y Neurocirugia, Mexico City, Mexico
cp Universidad Nacional Autónoma de México, Mexico City, Mexico
cq Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia
cr Tribhuvan University, Kirtipur, Nepal
cs University of Otago, Dunedin, New Zealand
ct University of Lagos, Lagos, Nigeria
cu College of Medicine of the University of Lagos, Lagos, Nigeria
cv Norwegian University of Science and Technology, Trondheim, Norway
cw Oslo University Hospital, Oslo, Norway
cx University of Science and Technology Bannu, Bannu, Pakistan
cy Universidad Cientifica del Sur, Lima, Peru
cz Metropolitan Medical Center, Manila, Philippines
da University of Puerto Rico, San Juan, Puerto Rico
db Research Center of Neurology, Moscow, Russian Federation
dc King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
dd King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
de University of KwaZulu-Natal, Durban, South Africa
df Stellenbosch University, Stellenbosch, South Africa
dg Seoul National University Hospital, Seoul, South Korea
dh Yongin Severance Hospital, Seoul, South Korea
di Hospital Universitario Burgos, Burgos, Spain
dj University Hospital Mutua Terrassa, Barcelona, Spain
dk Institut de Recerca Sant Joan de Deu, Barcelona, Spain
dl Research Institute Germans Trias i Pujol, Barcelona, Spain
dm Instituto de Biomedicina de Sevilla, Seville, Spain
dn University Hospital Germans Trias i Pujol, Barcelona, Spain
do Faculty of medicine university of Khartoum, Khartoum, Sudan
dp Lund University, Lund, Sweden
dq Inselspital Bern, University of Bern, Bern, Switzerland
dr University Hospital Bern, Bern, Switzerland
ds National Taiwan University Hospital, Taipei City, Taiwan
dt Chang Gung Memorial Hospital, Taoyuan City, Taiwan
du National Taiwan University, Taipei City, Taiwan
dv National Institute Mongi Ben Hamida of Neurology, Tunis, Tunisia
dw Mongi Ben Hmida National Institute of Neurology, Tunis, Tunisia
dx Koç University, Istanbul, Turkey
dy Şişli Etfal Training and Research Hospital, Istanbul, Turkey
dz University of Plymouth, Plymouth, United Kingdom
ea Parkinson’s UK, London, United Kingdom
eb University of Glasgow, Glasgow, United Kingdom
ec Cardiff University, Cardiff, United Kingdom
ed Royal Veterinary College University of London, London, United Kingdom
ee University of Bristol, Bristol, United Kingdom
ef Cure Parkinson’s, London, United Kingdom
eg University of Cincinnati, Cincinnati, OH, United States
eh The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, United States
ei Augusta University / University of Georgia Medical Partnership, Augusta, GA, United States
ej Mid-Atlantic Permanente Medical Group, Bethesda, MD, United States
ek Washington University, St. Louis, MO, United States
el Indiana University, Bloomington, IN, United States
em Rush University, Chicago, IL, United States
en Kaiser Permanente, Oakland, CA, United States
eo Coalition for Aligning Science, Washington, WA, United States
ep Banner Sun Health Research Institute, Sun City, AZ, United States
eq Michigan State University, East Lansing, MI, United States
er Northwestern University, Evanston, IL, United States
es Baylor College of Medicine, Houston, TX, United States
et Texas Children’s Hospital, Houston, TX, United States
eu University of Miami Miller School of Medicine, Miami, FL, United States
ev Beth Israel Deaconess Medical Center, Boston, MA, United States
ew North Shore University Health System, Chicago, IL, United States
ex Institute for Neurodegenerative Disorders, New Haven, CT, United States
ey University of Pittsburgh, Pittsburgh, PA, United States
ez Washington University, Saint Louis, MO, United States
fa University of Alabama at Birmingham, Birmingham, AL, United States
fb University of Maryland, Baltimore, MD, United States
fc University of Michigan, Ann Arbor, MI, United States
fd Columbia University, New York, NY, United States
fe James J. Peters Veterans Affairs Medical Center, New York, NY, United States
ff Aligning Science Across Parkinson’s, Washington, WA, United States
fg University of Chicago, Chicago, IL, United States
fh Indiana University School of Medicine, Indianapolis, IN, United States
fi Hue University, Huế, Viet Nam
fj University of Zambia, Lusaka, Zambia
Abstract
Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Funding details
MOH-000207, MOH-000559
MOE-MOET32020-0004, MOE-T2EP30220-0005
National Institutes of HealthNIH
U.S. Department of Health and Human ServicesHHS
National Institute on AgingNIA
National Institute of Neurological Disorders and StrokeNINDSR01NS112499, ZIA AG000949, ZO1 AG000535
Michael J. Fox Foundation for Parkinson’s ResearchMJFF
American Parkinson Disease AssociationAPDA
Aligning Science Across Parkinson’sASAP
Document Type: Article
Publication Stage: Article in Press
Source: Scopus