Hope Center Member Publications

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