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1. Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia.

Author

Manzoni, Claudia, Kia, Demis, Ferrari, Raffaele, Leonenko, Ganna, Costa, Beatrice, Saba, Valentina, Jabbari, Edwin, Tan, Manuela, Albani, Diego, Alvarez, Victoria, Alvarez, Ignacio, Andreassen, Ole, Angiolillo, Antonella, Arighi, Andrea, Baker, Matt, Benussi, Luisa, Bessi, Valentina, Binetti, Giuliano, Blackburn, Daniel, Boada, Merce, Boeve, Bradley, Borrego-Ecija, Sergi, Borroni, Barbara, Bråthen, Geir, Brooks, William, Bruni, Amalia, Caroppo, Paola, Bandres-Ciga, Sara, Clarimon, Jordi, Colao, Rosanna, Cruchaga, Carlos, Danek, Adrian, de Boer, Sterre, de Rojas, Itziar, di Costanzo, Alfonso, Dickson, Dennis, Diehl-Schmid, Janine, Dobson-Stone, Carol, Dols-Icardo, Oriol, Donizetti, Aldo, Dopper, Elise, Durante, Elisabetta, Ferrari, Camilla, Forloni, Gianluigi, Frangipane, Francesca, Fratiglioni, Laura, Kramberger, Milica, Galimberti, Daniela, Gallucci, Maurizio, García-González, Pablo, Ghidoni, Roberta, Giaccone, Giorgio, Graff, Caroline, Graff-Radford, Neill, Grafman, Jordan, Halliday, Glenda, Hernandez, Dena, Hjermind, Lena, Hodges, John, Holloway, Guy, Huey, Edward, Illán-Gala, Ignacio, Josephs, Keith, Knopman, David, Kristiansen, Mark, Kwok, John, Leber, Isabelle, Leonard, Hampton, Libri, Ilenia, Lleo, Alberto, Mackenzie, Ian, Madhan, Gaganjit, Maletta, Raffaele, Marquié, Marta, Maver, Ales, Menendez-Gonzalez, Manuel, Milan, Graziella, Miller, Bruce, Morris, Christopher, Morris, Huw, Nacmias, Benedetta, Newton, Judith, Nielsen, Jørgen, Nilsson, Christer, Novelli, Valeria, Padovani, Alessandro, Pal, Suvankar, Pasquier, Florence, Pastor, Pau, Perneczky, Robert, Peterlin, Borut, Petersen, Ronald, Piguet, Olivier, Pijnenburg, Yolande, Puca, Annibale, Rademakers, Rosa, Rainero, Innocenzo, Reus, Lianne, Richardson, Anna, and Riemenschneider, Matthias

Subjects
Humans, Frontotemporal Dementia, tau Proteins, Genome-Wide Association Study, Apolipoproteins E, Male, Female, Genetic Predisposition to Disease, Aged, Polymorphism, Single Nucleotide, Genetic Loci, Middle Aged, Case-Control Studies, Myelin Proteins
Abstract

Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10-12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10-12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10-8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.

Published
2024

2. Genome-wide determinants of mortality and motor progression in Parkinson’s disease

Author

Tan, Manuela M. X., Lawton, Michael A., Pollard, Miriam I., Brown, Emmeline, Real, Raquel, Carrasco, Alejandro Martinez, Bekadar, Samir, Jabbari, Edwin, Reynolds, Regina H., Iwaki, Hirotaka, Blauwendraat, Cornelis, Kanavou, Sofia, Hubbard, Leon, Malek, Naveed, Grosset, Katherine A., Bajaj, Nin, Barker, Roger A., Burn, David J., Bresner, Catherine, Foltynie, Thomas, Wood, Nicholas W., Williams-Gray, Caroline H., Andreassen, Ole A., Toft, Mathias, Elbaz, Alexis, Artaud, Fanny, Brice, Alexis, Corvol, Jean-Christophe, Aasly, Jan, Farrer, Matthew J., Nalls, Michael A., Singleton, Andrew B., Williams, Nigel M., Ben-Shlomo, Yoav, Hardy, John, Hu, Michele T. M., Grosset, Donald G., Shoai, Maryam, Pihlstrøm, Lasse, and Morris, Huw R.

Published
2024
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4. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author

Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martinez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernandez, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, and Morris, Huw R.

Published
2023
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6. Author Correction: The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author

Leonard, Hampton L., Murtadha, Ruqaya, Martinez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martinez, Ana-Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Alvarez Jerez, Pilar, Saini, Prabhjyot, al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, and Noyce, Alastair J.

Published
2023
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7. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author

Leonard, Hampton L., Murtadha, Ruqaya, Martinez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martinez, Ana-Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Alvarez Jerez, Pilar, Saini, Prabhjyot, al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, and Noyce, Alastair J.

Published
2023
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8. Genetic Stratification of Age‐Dependent Parkinson's Disease Risk by Polygenic Hazard Score

Author

Pihlstrøm, Lasse, Fan, Chun C, Frei, Oleksandr, Tan, Manuela, Karunamuni, Roshan A, Blauwendraat, Cornelis, Bandres‐Ciga, Sara, Gan‐Or, Ziv, Grosset, Donald G, Consortium, International Parkinson's Disease Genomics, Dale, Anders M, Seibert, Tyler M, and Andreassen, Ole A

Subjects
Neurodegenerative, Aging, Brain Disorders, Neurosciences, Prevention, Patient Safety, Parkinson's Disease, Detection, screening and diagnosis, Aetiology, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Neurological, Biomarkers, Humans, Incidence, Multifactorial Inheritance, Parkinson Disease, Risk Factors, Parkinson's disease, age at onset, genetics, polygenic score, prediction, International Parkinson's Disease Genomics Consortium, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundParkinson's disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders.ObjectivesWe aimed to develop and validate a polygenic hazard score model in sporadic PD.MethodsUsing a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls.ResultsA polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups.ConclusionsWe demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

9. Genetic Stratification of Age-Dependent Parkinson's Disease Risk by Polygenic Hazard Score.

Author

Pihlstrøm, Lasse, Fan, Chun C, Frei, Oleksandr, Tan, Manuela, Karunamuni, Roshan A, Blauwendraat, Cornelis, Bandres-Ciga, Sara, Gan-Or, Ziv, Grosset, Donald G, International Parkinson's Disease Genomics Consortium (IPDGC), Dale, Anders M, Seibert, Tyler M, and Andreassen, Ole A

Subjects
International Parkinson's Disease Genomics Consortium, Parkinson's disease, age at onset, genetics, polygenic score, prediction, Neurodegenerative, Prevention, Aging, Parkinson's Disease, Neurosciences, Patient Safety, Brain Disorders, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Neurology & Neurosurgery, Clinical Sciences, Human Movement and Sports Sciences
Abstract

BackgroundParkinson's disease (PD) is a highly age-related disorder, where common genetic risk variants affect both disease risk and age at onset. A statistical approach that integrates these effects across all common variants may be clinically useful for individual risk stratification. A polygenic hazard score methodology, leveraging a time-to-event framework, has recently been successfully applied in other age-related disorders.ObjectivesWe aimed to develop and validate a polygenic hazard score model in sporadic PD.MethodsUsing a Cox regression framework, we modeled the polygenic hazard score in a training data set of 11,693 PD patients and 9841 controls. The score was then validated in an independent test data set of 5112 PD patients and 5372 controls and a small single-study sample of 360 patients and 160 controls.ResultsA polygenic hazard score predicts the onset of PD with a hazard ratio of 3.78 (95% confidence interval 3.49-4.10) when comparing the highest to the lowest risk decile. Combined with epidemiological data on incidence rate, we apply the score to estimate genetically stratified instantaneous PD risk across age groups.ConclusionsWe demonstrate the feasibility of a polygenic hazard approach in PD, integrating the genetic effects on disease risk and age at onset in a single model. In combination with other predictive biomarkers, the approach may hold promise for risk stratification in future clinical trials of disease-modifying therapies, which aim at postponing the onset of PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2021

10. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

Author

Okubadejo, Njideka, Ojo, Oluwadamilola, Abiodun, Oladunni, Achoru, Charles, Agabi, Osigwe, Agulanna, Uchechi, Akinyemi, Rufus, Ali, Mohammed, Ani-Osheku, Ifeyinwa, Arigbodi, Ohwotemu, Bello, Abiodun, Erameh, Cyril, Farombi, Temitope, Fawale, Michael, Imarhiagbe, Frank, Iwuozo, Emmanuel, Komolafe, Morenikeji, Nwani, Paul, Nwazor, Ernest, Nyandaiti, Yakub, Obiabo, Yahaya, Odeniyi, Olanike, Odiase, Francis, Ojini, Francis, Onwuegbuzie, Gerald, Osaigbovo, Godwin, Osemwegie, Nosakhare, Oshinaike, Olajumoke, Otubogun, Folajimi, Oyakhire, Shyngle, Ozomma, Simon, Samuel, Sarah, Taiwo, Funmilola, Wahab, Kolawole, Zubair, Yusuf, Gams Massi, Daniel, Gueumekane Bila lamou, Eric, Njamnshi Nfor, Leonard, Magnerou, Mélanie Annick, Fogang Fogoum, Yannick, Shalash, Ali, El-FawaI, Hassan, Khedr, Eman, Fawi, Gharib, A. Eltantawi, Mohamed, Salama, Mohamed, El-Jaafary, Shaimaa, Hamed, Sharifa, Tafesse Mengesha, Abenet, Alemayehu Ayele, Biniyam, Melka Oda, Dereje, Zenebe Zewde, Yared, Debebe Gelan, Yohanesse, AkpaIu, Albert, Charway-Felli, Augustina, Stephen Sarfo, Fred, Adjei, Patrick, Obese, Vida, Bocoum, Abdoulaye, Koita, Abdou, Oumar Guinto, Cheick, Coulibaly, Toumany, Maiga, Youssoufa, Kone, Zaynab, Bell, Abiodun, Adebowale, Akintunde A., Akpekpe, John, lyagba, Alagoma, Wulgo, Ali Mohammed, Arabambi, Babawale, Agu, Christian, Dike, Franklin, Ishola, Ismail, Abiodun, Kehinde, Ekenze, Oluchi, Agabi Osigwe, Paul, Balarabe, Salisu, Abubakar, Sani, Williams, Uduak, Fall, Maouly, Mamadou Diop, Alassane, Hilaire Dominique, Ewodo Touna, Mochan, Andre, Modi, Girish, Dindayal, Saiesha, Ali Awadelkareem, Eman, Elsayed, Inas, Dahawi, Maha, Awadelkareem, Mosab Ali, Misbah, Sarah, Mushengez, Brighton, Kimambo, Henrika, Msango, Leonard, Adebayo, Philip, OKeng, Kigocha, Diekker, Marieke, URassa, Sarah, Gouider, Riadh, Ben Djebara, Mouna, Gargouri, Amina, Kacem, Imen, Nasri, Amina, Mrabet, Saloua, Sghaier, Ikram, Mkada, Imen, Atadzhanov, Masharip, Chishimba, Lorraine, Rizig, Mie, Jama, Fatumah, Okunoye, Olaitan, Hardy, John, Houlden, Henry, Singleton, Andrew, Nalls, Mike, Shamim, Ejaz, Jonas, Cabell, Williamson, Jared, Hall, Deborah A., Rosenbaum, Marc, Davis, Staci, Dean, Marissa, Cromer, Candace, Smith, Jenna, Ruffrage, Lauren, Richardson, Joseph, Sipma, Rebeka, Xie, Tao, Padmanaban, Manesh, Warren, Natalie, Mercado, Tomas, Disbrow, Elizabeth, Chauppeta, Brian, Thomas-Dean, Fermine, Toms, Jamie, Lofton, Katelyn, Rawls, Ashley, Rizer, Kyle, Black, Nieci, Solle, Justin, O'Grady, Alyssa, Sherer, Todd, Fiske, Brian, Başak, A. Nazlı, Tan, Ai Huey, Noyce, Alastair, Akpalu, Albert, Espay, Alberto, Martínez-Carrasco, Alejandro, Medina, Alex, Zimprich, Alexander, Brice, Alexis, Karimova, Altynay, Hernandez, Alvaro, Illarionova, Anastasia, Quattrone, Andrea, Singleton, Andrew B, Sobering, Andrew K., Vinuela, Angel, Sanyaolu, Arinola, Schumacher-Schuh, Artur F., Kishore, Asha, Ahmad-Annuar, Azlina, Al Mubarak, Bashayer, Tang, Beisha, Pizarro Galleguillos, Benjamin, Jeon, Beomseok, Siddiqi, Bernadette, Casey, Bradford, Mollenhauer, Brit, Carroll, Camille, Rieder, Carlos, Pantazis, Caroline B., Comart, Charisse, Lin, Chin-Hsien, Klein, Christine, Bale, Claire, Shepherd, Claire E, Wegel, Claire, Blauwendraat, Cornelis, Vitale, Dan, Martinez-Ramirez, Daniel, Hall, Deborah, Hernandez, Dena, KP, Divya, Nguyen, Duan, Fon, Edward A., Dadiotis, Efthymios, Riley, Ekemini, Iakovenko, Elena, Stafford, Ellie, Gatto, Emilia M, Valente, Enza Maria, Vollstedt, Eva-Juliane, Faghri, Faraz, Genc, Gencer, Xiromerisiou, Georgia, Hadjigorgiou, Georgios, Hiu-Fai Chan, Germaine, Arboleda, Gonzalo, Kaishibayeva, Gulnaz, Höglinger, Günter, Leonard, Hampton, Madoev, Harutyun, Iwaki, Hirotaka, Chen, Honglei, Wu, Hsiu-Chuan, Shang, Huifang, Morris, Huw R, F. Mata, Ignacio, Keller Sarmiento, Ignacio Juan, Dagklis, Ioannis, Tarnanas, Ioannis, Aasly, Jan O., Hoenicka, Janet, Corvol, Jean-Christophe, Foo, Jia Nee, Guo, Jifeng, Junker, Johanna, Carr, Jonathan, Kim, Jonggeol Jeff, Orozco, Jorge, Jankovic, Joseph, Shulman, Joshua, Hunter, Julie, Solle, Justin C., Murphy, Kaileigh, Nuytemans, Karen, Kieburtz, Karl, Lohmann, Katja, Marek, Kenneth, Mok, Kin Ying, Kumar, Kishore, Levine, Kristin, Chahine, Lana M., Lange, Lara M., Pihlstrøm, Lasse, Screven, Laurel, Stefanis, Leonidas, Shulman, Lisa, Marsili, Luca, Parnetti, Lucilla, Kuhl, Maggie, Funayama, Manabu, Sharma, Manu, Tan, Manuela, Kauffman, Marcelo, Miranda, Marcelo, Bustamante, Maria Leonor, Stamelou, Maria, Periñan Tocino, Maria Teresa, Cornejo-Olivas, Mario, Jimenez del Rio, Marlene, Makarious, Mary B, Koretsky, Mathew, Rodriguez-Violante, Mayela, Ellis, Melina, Avenali, Micol, Rentería, Miguel E., Inca-Martines, Miguel z, Nalls, Mike A., Ibrahim Norlinah, Mohamed, Umair, Muhammad, Ip, Nancy, Louie, Naomi, Cheung, Nelson Yuk-Fai, Mencacci, Niccolò Emanuele, Wood, Nicholas, Williams, Nigel, Hattori, Nobutaka, Abdul Murad, Nor Azian, Ibrahim, Norlinah Mohamed, Monchi, Oury, Öztop Çakmak, Özgür, Öztop Çakmak, Patricio Öztop Çakmak, Lewis, Patrick Alfryn, Pastor, Pau, Reyes-Pérez, Paula, Saffie Awad, Paula, Chana, Pedro, Chan, Phillip, Kung, Pin-Jui, Chan, Piu, Pal, Pramod, Lingappa Kukkle, Prashanth, Ojha, Rajeev, Kaiyrzhanov, Rauan, Krüger, Rejko, Amouri, Rim, Weil, Rimona, Rajan, Roopa, Alcalay, Roy, Wu, Ruey-Meei, Borgohain, Rupam, Sassi, Samia Ben, Khachatryan, Samson, Bandres-Ciga, Sara, El-Sadig, Sarah, Wu, Serena, Groppa, Sergio, Azmin, Shahrul, Lim, Shen-Yang, Ur-Rehman, Shoaib, Ertan, Sibel, Stott, Simon, Jasaitye, Simona, Chowdhury, Sohini, Dumanis, Sonya, Bardien, Soraya, Lubbe, Steven, Koks, Sulev, Dey, Sumit, Foroud, Tatiana, Fon, Ted, Beach, Thomas, Gasser, Thomas, Anderson, Tim, Nguyen, Toan, Schirinzi, Tommaso, Shiraishi, Tomotaka, Pitcher, Toni, Tumas, Vitor, Mohamed, Wael, Kamel, Walaa A., Luo, Wei, Zhou, Xiaopu, Zewde, Yared Z., Song, Yeajin, Wen, Yi, Wu, Yihru, Joong Kim, Yun, Tavadyan, Zaruhi, Fang, Zih-Hua, Ojo, Oluwadamilola Omolara, Crea, Peter Wild, Abiodun, Oladunni Victoria, Levine, Kristin S, Abubakar, Sani Atta, Achoru, Charles Obiora, Adeniji, Olaleye Akinmola, Agabi, Osigwe Paul, Koretsky, Mathew J, Hall, Deborah A, Akinyemi, Rufus Olusola, Ali, Mohammed Wulgo, Shamim, Ejaz A, Padmanaban, Mahesh, Arigbodi, Ohwotemu Michael, Standaert, David G, Bello, Abiodun Hamzat, Dean, Marissa N, Erameh, Cyril Oshomah, Farombi, Temitope Hannah, Fawale, Michael Bimbola, Billingsley, Kimberley J, Imarhiagbe, Frank Aiwansoba, Jerez, Pilar Alvarez, Iwuozo, Emmanuel Uzodinma, Baker, Breeana, Komolafe, Morenikeji Adeyoyin, Malik, Laksh, Nwani, Paul Osemeke, Daida, Kensuke, Nwazor, Ernest Okwundu, Miano-Burkhardt, Abigail, Nyandaiti, Yakub Wilberforce, Obiabo, Yahaya Olugbo, Kluss, Jillian H, Odeniyi, Olanike Adedoyin, Hernandez, Dena G, Odiase, Francis Ehidiamen, Tayebi, Nahid, Ojini, Francis Ibe, Sidranksy, Ellen, Onwuegbuzie, Gerald Awele, D'Souza, Andrea M, Osaigbovo, Godwin Osawaru, Berhe, Bahafta, Reed, Xylena, Oshinaike, Olajumoke Olufemi, Leonard, Hampton L, Otubogun, Folajimi Morenikeji, Alvarado, Chelsea X, Oyakhire, Shyngle Imiewan, Ozomma, Simon Izuchukwu, Samuel, Sarah Chabiri, Taiwo, Funmilola Tolulope, Wahab, Kolawole Wasiu, Zubair, Yusuf Agboola, Kim, Jonggeol Jeffrey, Nalls, Mike A, Heilbron, Karl, Norcliffe-Kaufmann, Lucy, and Okubadejo, Njideka Ulunma

Published
2023
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11. Identifying genetic determinants of progression in Parkinson's disease

Author

Tan, Manuela Mei Xuan

Subjects
616.8
Abstract

Parkinson's disease (PD) is a progressive neurodegenerative condition for which there are currently no treatments to stop or slow disease progression. A number of genome-wide association studies (GWASs) of PD patients compared to controls have identified genetic variants associated with disease risk, however these cannot inform us about the genetic factors and biology underpinning progression. The aim of this PhD is to identify genetic variants associated with disease progression. I first examined the frequency and baseline clinical features of patients carrying rare pathogenic Mendelian mutations (including variants in LRRK2, SNCA, Parkin, and PINK1) in the Tracking Parkinson's cohort. I showed that Parkin and PINK1 carriers had better cognition than other early-onset patients at baseline despite having longer disease duration, suggesting slower progression. In analysis of longitudinal data, I also showed that GBA carriers appeared to have more rapid motor and cognitive progression than non-carriers. Prior to conducting GWASs, I sought to understand the clinical predictors of progression and showed that age at onset and gender were associated with progression to clinical milestones. Following a new method from the Huntington's disease progression GWAS, I used principal components analysis (PCA) to combine multiple motor and cognitive scales in PD to create composite progression scores. I showed that APOE ε4 was strongly associated with cognitive progression, and identified a novel signal in ATP8B2 which was nominally associated with motor progression. Finally, I conducted large-scale GWASs of survival to clinical milestones: mortality, Hoehn and Yahr stage 3, and dementia, using data from Tracking Parkinson's, Oxford Discovery, Parkinson's Progression Markers Initiative, Queen Square Brain Bank, UK Biobank, and Calypso studies. I identified loci in or near APOE, ADRA2A, and SH3GL2 which were nominally associated with progression to mortality. I also showed that the APOE ε4 variant, rs429358, was strongly associated with progression to dementia.

Published
2021

12. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Author

Nalls, Mike A, Blauwendraat, Cornelis, Vallerga, Costanza L, Heilbron, Karl, Bandres-Ciga, Sara, Chang, Diana, Tan, Manuela, Kia, Demis A, Noyce, Alastair J, Xue, Angli, Bras, Jose, Young, Emily, von Coelln, Rainer, Simón-Sánchez, Javier, Schulte, Claudia, Sharma, Manu, Krohn, Lynne, Pihlstrøm, Lasse, Siitonen, Ari, Iwaki, Hirotaka, Leonard, Hampton, Faghri, Faraz, Gibbs, J Raphael, Hernandez, Dena G, Scholz, Sonja W, Botia, Juan A, Martinez, Maria, Corvol, Jean-Christophe, Lesage, Suzanne, Jankovic, Joseph, Shulman, Lisa M, Sutherland, Margaret, Tienari, Pentti, Majamaa, Kari, Toft, Mathias, Andreassen, Ole A, Bangale, Tushar, Brice, Alexis, Yang, Jian, Gan-Or, Ziv, Gasser, Thomas, Heutink, Peter, Shulman, Joshua M, Wood, Nicholas W, Hinds, David A, Hardy, John A, Morris, Huw R, Gratten, Jacob, Visscher, Peter M, Graham, Robert R, Singleton, Andrew B, Team, 23andMe Research, Consortium, System Genomics of Parkinson's Disease, Consortium, International Parkinson's Disease Genomics, Adarmes-Gómez, Astrid D, Aguilar, Miquel, Aitkulova, Akbota, Akhmetzhanov, Vadim, Alcalay, Roy N, Alvarez, Ignacio, Alvarez, Victoria, Barrero, Francisco Javier, Yarza, Jesús Alberto Bergareche, Bernal-Bernal, Inmaculada, Billingsley, Kimberley, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Brockmann, Kathrin, Bubb, Vivien, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Chelban, Viorica, Clarimón, Jordi, Clarke, Carl, Compta, Yaroslau, Cookson, Mark R, Craig, David W, Danjou, Fabrice, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Escott-Price, Valentina, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, and Finkbeiner, Steven

Subjects
Neurosciences, Parkinson's Disease, Brain Disorders, Aging, Biotechnology, Prevention, Genetics, Human Genome, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Databases, Genetic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Parkinson Disease, Risk Factors, 23andMe Research Team, System Genomics of Parkinson's Disease Consortium, International Parkinson's Disease Genomics Consortium, Clinical Sciences, Neurology & Neurosurgery
Abstract

BackgroundGenome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease.MethodsWe did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation.FindingsBetween Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16-36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10-7).InterpretationThese data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data.FundingThe National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources).

Published
2019

14. The genetic and clinico-pathological profile of early-onset progressive supranuclear palsy.

Author

Jabbari, Edwin, Woodside, John, Tan, Manuela, Pavese, Nicola, Bandmann, Oliver, Ghosh, Boyd, Massey, Luke, Capps, Erica, Warner, Tom, Lees, Andrew, Revesz, Tamas, Holton, Janice, Williams, Nigel, Grosset, Donald, and Morris, Huw

Subjects
Parkinsons disease/parkinsonism, clinical neurology, genetics, progressive supranuclear palsy, Adult, Age of Onset, Aged, Aged, 80 and over, Diagnosis, Differential, Disease Progression, Female, Gait Disorders, Neurologic, Genetic Testing, Genotype, Humans, Male, Middle Aged, Parkinson Disease, Predictive Value of Tests, Supranuclear Palsy, Progressive, Tissue Banks, Young Adult
Abstract

BACKGROUND: Studies on early-onset presentations of progressive supranuclear palsy (PSP) have been limited to those where a rare monogenic cause has been identified. Here, we have defined early-onset PSP (EOPSP) and investigated its genetic and clinico-pathological profile in comparison with late-onset PSP (LOPSP) and Parkinsons disease (PD). METHODS: We included subjects from the Queen Square Brain Bank, PROSPECT-UK study, and Tracking Parkinsons study. Group comparisons of data were made using Welchs t-test and Kruskal-Wallis analysis of variance. EOPSP was defined as the youngest decile of motor age at onset (≤55 years) in the Queen Square Brain Bank PSP case series. RESULTS: We identified 33 EOPSP, 328 LOPSP, and 2000 PD subjects. The early clinical features of EOPSP usually involve limb parkinsonism and gait freezing, with 50% of cases initially misdiagnosed as having PD. We found that an initial clinical diagnosis of EOPSP had lower diagnostic sensitivity (33%) and positive predictive value (38%) in comparison with LOPSP (80% and 76%) using a postmortem diagnosis of PSP as the gold standard. 3/33 (9%) of the EOPSP group had an underlying monogenic cause. Using a PSP genetic risk score (GRS), we showed that the genetic risk burden in the EOPSP (mean z-score, 0.59) and LOPSP (mean z-score, 0.48) groups was significantly higher (P

Published
2019

15. The endocytic membrane trafficking pathway plays a major role in the risk of Parkinson's disease

Author

Bandres‐Ciga, Sara, Saez‐Atienzar, Sara, Bonet‐Ponce, Luis, Billingsley, Kimberley, Vitale, Dan, Blauwendraat, Cornelis, Gibbs, Jesse Raphael, Pihlstrøm, Lasse, Gan‐Or, Ziv, Noyce, Alastair J, Kaiyrzhanov, Rauan, Middlehurst, Ben, Kia, Demis A, Tan, Manuela, Houlden, Henry, Morris, Huw R, Plun‐Favreau, Helene, Holmans, Peter, Hardy, John, Trabzuni, Daniah, Bras, Jose, Quinn, John, Mok, Kin Y, Kinghorn, Kerri J, Wood, Nicholas W, Lewis, Patrick, Schreglmann, Sebastian, Guerreiro, Rita, Lovering, Ruth, RņBibo, Lea, Manzoni, Claudia, Rizig, Mie, Ryten, Mina, Guelfi, Sebastian, Escott‐Price, Valentina, Chelban, Viorica, Foltynie, Thomas, Williams, Nigel, Morrison, Karen E, Brice, Alexis, Danjou, Fabrice, Lesage, Suzanne, Corvol, Jean‐Christophe, Martinez, Maria, Schulte, Claudia, Brockmann, Kathrin, SimɃn‐Sȥnchez, Javier, Heutink, Peter, Rizzu, Patrizia, Sharma, Manu, Gasser, Thomas, Nicolas, Aude, Cookson, Mark R, Craig, David W, Faghri, Faraz, Gibbs, J Raphael, Hernandez, Dena G, Van Keuren‐Jensen, Kendall, Shulman, Joshua M, Iwaki, Hirotaka, Leonard, Hampton L, Nalls, Mike A, Robak, Laurie, Lubbe, Steven, Finkbeiner, Steven, Mencacci, Niccolo E, Lungu, Codrin, Singleton, Andrew B, Scholz, Sonja W, Reed, Xylena, Alcalay, Roy N, Rouleau, Guy A, Hilten, Jacobus J, Marinus, Johan, Adarmes‐GɃmez, Astrid D, Aguilar, Miquel, Alvarez, Ignacio, Alvarez, Victoria, Barrero, Francisco Javier, Yarza, Jesɐs Alberto Bergareche, Bernal‐Bernal, Inmaculada, Blazquez, Marta, Bonilla‐Toribio, Marta, Botȷa, Juan A, Boungiorno, Marȷa Teresa, Buiza‐Rueda, Dolores, Cȥmara, Ana, Carrillo, Fȥtima, CarriɃn‐Claro, Mario, Cerdan, Debora, ClarimɃn, Jordi, Compta, Yaroslau, Casa, Beatrȷz, Diez‐Fairen, Monica, Dols‐Icardo, Oriol, and Duarte, Jacinto

Subjects
Parkinson's Disease, Human Genome, Genetics, Neurosciences, Brain Disorders, Prevention, Neurodegenerative, Genetic Testing, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Aetiology, Decent Work and Economic Growth, Endocytosis, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Parkinson Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Risk Factors, International Parkinson's Disease Genomics Consortium, Parkinson's disease, endocytosis, genetic risk, heritability, polygenic risk score, Clinical Sciences, Human Movement and Sports Sciences, Neurology & Neurosurgery
Abstract

BackgroundPD is a complex polygenic disorder. In recent years, several genes from the endocytic membrane-trafficking pathway have been suggested to contribute to disease etiology. However, a systematic analysis of pathway-specific genetic risk factors is yet to be performed.ObjectivesTo comprehensively study the role of the endocytic membrane-trafficking pathway in the risk of PD.MethodsLinkage disequilibrium score regression was used to estimate PD heritability explained by 252 genes involved in the endocytic membrane-trafficking pathway including genome-wide association studies data from 18,869 cases and 22,452 controls. We used pathway-specific single-nucleotide polymorphisms to construct a polygenic risk score reflecting the cumulative risk of common variants. To prioritize genes for follow-up functional studies, summary-data based Mendelian randomization analyses were applied to explore possible functional genomic associations with expression or methylation quantitative trait loci.ResultsThe heritability estimate attributed to endocytic membrane-trafficking pathway was 3.58% (standard error = 1.17). Excluding previously nominated PD endocytic membrane-trafficking pathway genes, the missing heritability was 2.21% (standard error = 0.42). Random heritability simulations were estimated to be 1.44% (standard deviation = 0.54), indicating that the unbiased total heritability explained by the endocytic membrane-trafficking pathway was 2.14%. Polygenic risk score based on endocytic membrane-trafficking pathway showed a 1.25 times increase of PD risk per standard deviation of genetic risk. Finally, Mendelian randomization identified 11 endocytic membrane-trafficking pathway genes showing functional consequence associated to PD risk.ConclusionsWe provide compelling genetic evidence that the endocytic membrane-trafficking pathway plays a relevant role in disease etiology. Further research on this pathway is warranted given that critical effort should be made to identify potential avenues within this biological process suitable for therapeutic interventions. © 2019 International Parkinson and Movement Disorder Society.

Published
2019

16. Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Author

Adarmes-Gómez, Astrid D, Aguilar, Miquel, Aitkulova, Akbota, Akhmetzhanov, Vadim, Alcalay, Roy N, Alvarez, Ignacio, Alvarez, Victoria, Bandres-Ciga, Sara, Barrero, Francisco Javier, Bergareche Yarza, Jesús Alberto, Bernal-Bernal, Inmaculada, Billingsley, Kimberley, Blauwendraat, Cornelis, Blazquez, Marta, Bonilla-Toribio, Marta, Botía, Juan A, Boungiorno, María Teresa, Bras, Jose, Brice, Alexis, Brockmann, Kathrin, Bubb, Vivien, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, Mario, Cerdan, Debora, Chelban, Viorica, Clarimón, Jordi, Clarke, Carl, Compta, Yaroslau, Cookson, Mark R, Corvol, Jean-Christophe, Craig, David W, Danjou, Fabrice, Diez-Fairen, Monica, Dols-Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Escott-Price, Valentina, Ezquerra, Mario, Faghri, Faraz, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Finkbeiner, Steven, Foltynie, Thomas, Gan-Or, Ziv, Garcia, Ciara, García-Ruiz, Pedro, Gasser, Thomas, Gibbs, J Raphael, Gomez Heredia, Maria Jose, Gómez-Garre, Pilar, González, Manuel Menéndez, Gonzalez-Aramburu, Isabel, Guelfi, Sebastian, Guerreiro, Rita, Hardy, John, Hassin-Baer, Sharon, Hernandez, Dena G, Heutink, Peter, Hoenicka, Janet, Holmans, Peter, Houlden, Henry, Infante, Jon, Iwaki, Hirotaka, Jesús, Silvia, Jimenez-Escrig, Adriano, Kaishybayeva, Gulnaz, Kaiyrzhanov, Rauan, Karimova, Altynay, Kia, Demis A, Kinghorn, Kerri J, Koks, Sulev, Krohn, Lynne, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Leonard, Hampton L, Lesage, Suzanne, Lewis, Patrick, Lopez-Sendon, Jose Luis, Lovering, Ruth, Lubbe, Steven, Lungu, Codrin, Macias, Daniel, Majamaa, Kari, Manzoni, Claudia, Marín, Juan, Marinus, Johan, Marti, Maria Jose, Martinez, Maria, Martínez Torres, Irene, Martínez-Castrillo, Juan Carlos, Mata, Marina, Mencacci, Niccolo E, Méndez-del-Barrio, Carlota, Middlehurst, Ben, Mínguez, Adolfo, Mir, Pablo, Mok, Kin Y, Morris, Huw R, Muñoz, Esteban, Nalls, Mike A, Narendra, Derek, Noyce, Alastair J, Ojo, Oluwadamilola O, Okubadejo, Njideka U, Pagola, Ana Gorostidi, Pastor, Pau, Perez Errazquin, Francisco, Periñán-Tocino, Teresa, Pihlstrom, Lasse, Plun-Favreau, Helene, Quinn, John, R'Bibo, Lea, Reed, Xylena, Rezola, Elisabet Mondragon, Rizig, Mie, Rizzu, Patrizia, Robak, Laurie, Rodriguez, Antonio Sanchez, Rouleau, Guy A, Ruiz-Martínez, Javier, Ruz, Clara, Ryten, Mina, Sadykova, Dinara, Scholz, Sonja W, Schreglmann, Sebastian, Schulte, Claudia, Sharma, Manu, Shashkin, Chingiz, Shulman, Joshua M, Sierra, María, Siitonen, Ari, Simón-Sánchez, Javier, Singleton, Andrew B, Suarez-Sanmartin, Esther, Taba, Pille, Tabernero, Cesar, Tan, Manuela X, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Toft, Mathias, Tolosa, Eduard, Trabzuni, Daniah, Valldeoriola, Francesc, van Hilten, Jacobus J, Van Keuren-Jensen, Kendall, Vargas-González, Laura, Vela, Lydia, Vives, Francisco, Williams, Nigel, Wood, Nicholas W, Zharkinbekova, Nazira, Zharmukhanov, Zharkyn, Zholdybayeva, Elena, Zimprich, Alexander, Ylikotila, Pauli, Shulman, Lisa M., von Coelln, Rainer, Reich, Stephen, Savitt, Joseph, Agee, Michelle, Alipanahi, Babak, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Elson, Sarah L., Fontanillas, Pierre, Furlotte, Nicholas A., Huber, Karen E., Hicks, Barry, Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., McCreight, Jennifer C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Noblin, Elizabeth S., Northover, Carrie A.M., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shelton, Janie F., Shringarpure, Suyash, Tian, Chao, Tung, Joyce, Vacic, Vladimir, Wang, Xin, Wilson, Catherine H., Anderson, Tim, Bentley, Steven, Dalrymple-Alford, John, Fowdar, Javed, Gratten, Jacob, Halliday, Glenda, Henders, Anjali K., Hickie, Ian, Kassam, Irfahan, Kennedy, Martin, Kwok, John, Lewis, Simon, Mellick, George, Montgomery, Grant, Pearson, John, Pitcher, Toni, Sidorenko, Julia, Silburn, Peter A., Vallerga, Costanza L., Visscher, Peter M., Wallace, Leanne, Wray, Naomi R., Xue, Angli, Yang, Jian, Zhang, Futao, Vallerga, Costanza L, Heilbron, Karl, Chang, Diana, Tan, Manuela, Young, Emily, Pihlstrøm, Lasse, Leonard, Hampton, Botia, Juan A, Jankovic, Joseph, Shulman, Lisa M, Sutherland, Margaret, Tienari, Pentti, Andreassen, Ole A, Bangale, Tushar, Hinds, David A, Hardy, John A, Visscher, Peter M, and Graham, Robert R

Published
2019
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17. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study

Author

Mok, Kin Y., Murphy, David P., Al-Sarraj, Safa, Troakes, Claire, Gentleman, Steve M., Allinson, Kieren S.J., Jaunmuktane, Zane, Holton, Janice L., Lees, Andrew J., Morris, Christopher M., Compta, Yaroslau, Gelpi, Ellen, van Swieten, John C., Rajput, Alex, Ferguson, Leslie, Cookson, Mark R., Gibbs, J. Raphael, Blauwendraat, Cornelis, Ding, Jinhui, Chia, Ruth, Traynor, Bryan J., Pantelyat, Alexander, Viollet, Coralie, Pletnikova, Olga, Troncoso, Juan C., Rosenthal, Liana S., Boxer, Adam L., Respondek, Gesine, Arzberger, Thomas, Roeber, Sigrun, Giese, Armin, Burn, David J., Pavese, Nicola, Gerhard, Alexander, Kobylecki, Christopher, Leigh, P. Nigel, Church, Alistair, T.M. Hu, Michele, Jabbari, Edwin, Koga, Shunsuke, Valentino, Rebecca R, Reynolds, Regina H, Ferrari, Raffaele, Tan, Manuela M X, Rowe, James B, Dalgard, Clifton L, Scholz, Sonja W, Dickson, Dennis W, Warner, Thomas T, Revesz, Tamas, Höglinger, Günter U, Ross, Owen A, Ryten, Mina, Hardy, John, Shoai, Maryam, and Morris, Huw R

Published
2021
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19. Parkinson’s Families Project: a UK-wide study of early onset and familial Parkinson’s disease

Author

Schmaderer, Theresa M., primary, Towns, Clodagh, additional, Jasaityte, Simona, additional, Tan, Manuela M. X., additional, Pollard, Miriam, additional, Hodgson, Megan, additional, Wu, Lesley, additional, Tilney, Russel, additional, Labrum, Robyn, additional, Hehir, Jason, additional, Polke, James, additional, Bhatia, Kailash P., additional, Houlden, Henry, additional, Wood, Nicholas W., additional, Jarman, Paul R., additional, Morris, Huw R., additional, and Real, Raquel, additional

Published
2023
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20. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author

Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, Global Parkinson’s Genetics Program, Michael J. Fox Foundation for Parkinson's Research, Aligning Science Against Parkinson's, National Institutes of Health (US), National Institute on Aging (US), National Institute of Neurological Disorders and Stroke (US), Leonard, Hampton [0000-0003-2390-8110], Illarionova, Anastasia [0000-0002-1711-7155], Moore, Anni [0000-0003-1953-6449], Bustos, Bernabé I. [0000-0003-2679-9503], Huxford, Brook [0000-0002-5908-6983], Storm, Catherine S. [0000-0003-4957-1712], Towns, Clodagh [0000-0001-8418-6241], Yu, Eric [0000-0003-3525-4564], Elsayed, Inas [0000-0003-4646-8218], Lake, Julie [0000-0002-3441-2455], Brolin, Kajsa [0000-0003-4832-922X], Senkevich, Konstantin [0000-0003-3407-5716], Tan, Manuela M. X. [0000-0001-5835-669X], Makarious, Mary B [.0000-0002-7978-1051], Pillay, Nikita Simone [0000-0002-9058-0920], Betancor, Oswaldo Lorenzo [0000-0002-5607-8363], Real, Raquel [0000-0001-8117-742X], Reynolds, Regina H. [0000-0001-6470-7919], Scotton, William J. [0000-0003-0607-3190], Singleton, Andrew [0000-0001-5606-700X], Dey, Sumit [0000-0002-9087-4486], Blauwendraat, Cornelis [0000-0001-9358-8111], Noyce, Alastair [0000-0003-3027-5497], Leonard, Hampton, Murtadha, Ruqaya, Martínez-Carrasco, Alejandro, Jama, Alina, Müller-Nedebock, Amica Corda, Gil-Martínez, Ana Luisa, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabé I., Jadhav, Bharati, Huxford, Brook, Storm, Catherine S., Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P., Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M. X., Periñán, María Teresa, Makarious, Mary B., Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R., Álvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Real, Raquel, Reynolds, Regina H., Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C., Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J., Song, Yeajin, Singleton, Andrew, Nalls, Mike A., Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair, International Parkinson’s Disease Genomics Consortium, and Global Parkinson’s Genetics Program

Abstract

Open science and collaboration are necessary to facilitate the advancement of Parkinson's disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.

Published
2023

21. Lysosomal Polygenic Burden Drives Cognitive Decline in Parkinson's Disease with Low Alzheimer Risk.

Author

Tunold, Jon‐Anders, Tan, Manuela M.X., Toft, Mathias, Ross, Owen, van de Berg, Wilma D.J., and Pihlstrøm, Lasse

Abstract

Background: Genetics influence cognitive progression in Parkinson's disease, possibly through mechanisms related to Lewy and Alzheimer's disease pathology. Lysosomal polygenic burden has recently been linked to more severe Lewy pathology post mortem. Objectives: To assess the influence of lysosomal polygenic burden on cognitive progression in Parkinson's disease patients with low Alzheimer's disease risk. Methods: Using Cox regression we assessed association between lysosomal polygenic scores and time to Montreal Cognitive Assessment score ≤ 21 in the Parkinson's Progression Markers Initiative cohort (n = 374), with replication in data from the Parkinson's Disease Biomarker Program (n = 777). Patients were stratified by Alzheimer's disease polygenic risk. Results: The lysosomal polygenic score was associated with faster progression of cognitive decline in patients with low Alzheimer's disease risk in both datasets (P = 0.0032 and P = 0.0054, respectively). Conclusion: Our study supports complex interplay between genetics and neuropathology in Parkinson's disease‐related cognitive impairment, emphasizing the role of lysosomal polygenic burden. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Genome-wide Analysis of Motor Progression in Parkinson Disease

Author

Martínez Carrasco, Alejandro, primary, Real, Raquel, additional, Lawton, Michael, additional, Hertfelder Reynolds, Regina, additional, Tan, Manuela, additional, Wu, Lesley, additional, Williams, Nigel, additional, Carroll, Camille, additional, Corvol, Jean-Christophe, additional, Hu, Michele, additional, Grosset, Donald, additional, Hardy, John, additional, Ryten, Mina, additional, Ben-Shlomo, Yoav, additional, Shoai, Maryam, additional, and Morris, Huw R., additional

Published
2023
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23. Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study

Author

Rizig, Mie, primary, Bandres-Ciga, Sara, additional, Makarious, Mary B, additional, Ojo, Oluwadamilola Omolara, additional, Crea, Peter Wild, additional, Abiodun, Oladunni Victoria, additional, Levine, Kristin S, additional, Abubakar, Sani Atta, additional, Achoru, Charles Obiora, additional, Vitale, Dan, additional, Adeniji, Olaleye Akinmola, additional, Agabi, Osigwe Paul, additional, Koretsky, Mathew J, additional, Agulanna, Uchechi, additional, Hall, Deborah A, additional, Akinyemi, Rufus Olusola, additional, Xie, Tao, additional, Ali, Mohammed Wulgo, additional, Shamim, Ejaz A, additional, Ani-Osheku, Ifeyinwa, additional, Padmanaban, Mahesh, additional, Arigbodi, Ohwotemu Michael, additional, Standaert, David G, additional, Bello, Abiodun Hamzat, additional, Dean, Marissa N, additional, Erameh, Cyril Oshomah, additional, Elsayed, Inas, additional, Farombi, Temitope Hannah, additional, Okunoye, Olaitan, additional, Fawale, Michael Bimbola, additional, Billingsley, Kimberley J, additional, Imarhiagbe, Frank Aiwansoba, additional, Jerez, Pilar Alvarez, additional, Iwuozo, Emmanuel Uzodinma, additional, Baker, Breeana, additional, Komolafe, Morenikeji Adeyoyin, additional, Malik, Laksh, additional, Nwani, Paul Osemeke, additional, Daida, Kensuke, additional, Nwazor, Ernest Okwundu, additional, Miano-Burkhardt, Abigail, additional, Nyandaiti, Yakub Wilberforce, additional, Fang, Zih-Hua, additional, Obiabo, Yahaya Olugbo, additional, Kluss, Jillian H, additional, Odeniyi, Olanike Adedoyin, additional, Hernandez, Dena G, additional, Odiase, Francis Ehidiamen, additional, Tayebi, Nahid, additional, Ojini, Francis Ibe, additional, Sidranksy, Ellen, additional, Onwuegbuzie, Gerald Awele, additional, D'Souza, Andrea M, additional, Osaigbovo, Godwin Osawaru, additional, Berhe, Bahafta, additional, Osemwegie, Nosakhare, additional, Reed, Xylena, additional, Oshinaike, Olajumoke Olufemi, additional, Leonard, Hampton L, additional, Otubogun, Folajimi Morenikeji, additional, Alvarado, Chelsea X, additional, Oyakhire, Shyngle Imiewan, additional, Ozomma, Simon Izuchukwu, additional, Samuel, Sarah Chabiri, additional, Taiwo, Funmilola Tolulope, additional, Wahab, Kolawole Wasiu, additional, Zubair, Yusuf Agboola, additional, Iwaki, Hirotaka, additional, Kim, Jonggeol Jeffrey, additional, Morris, Huw R, additional, Hardy, John, additional, Nalls, Mike A, additional, Heilbron, Karl, additional, Norcliffe-Kaufmann, Lucy, additional, Blauwendraat, Cornelis, additional, Houlden, Henry, additional, Singleton, Andrew, additional, Okubadejo, Njideka Ulunma, additional, Okubadejo, Njideka, additional, Ojo, Oluwadamilola, additional, Abiodun, Oladunni, additional, Achoru, Charles, additional, Agabi, Osigwe, additional, Akinyemi, Rufus, additional, Ali, Mohammed, additional, Arigbodi, Ohwotemu, additional, Bello, Abiodun, additional, Erameh, Cyril, additional, Farombi, Temitope, additional, Fawale, Michael, additional, Imarhiagbe, Frank, additional, Iwuozo, Emmanuel, additional, Komolafe, Morenikeji, additional, Nwani, Paul, additional, Nwazor, Ernest, additional, Nyandaiti, Yakub, additional, Obiabo, Yahaya, additional, Odeniyi, Olanike, additional, Odiase, Francis, additional, Ojini, Francis, additional, Onwuegbuzie, Gerald, additional, Osaigbovo, Godwin, additional, Oshinaike, Olajumoke, additional, Otubogun, Folajimi, additional, Oyakhire, Shyngle, additional, Ozomma, Simon, additional, Samuel, Sarah, additional, Taiwo, Funmilola, additional, Wahab, Kolawole, additional, Zubair, Yusuf, additional, Gams Massi, Daniel, additional, Gueumekane Bila lamou, Eric, additional, Njamnshi Nfor, Leonard, additional, Magnerou, Mélanie Annick, additional, Fogang Fogoum, Yannick, additional, Shalash, Ali, additional, El-FawaI, Hassan, additional, Khedr, Eman, additional, Fawi, Gharib, additional, A. Eltantawi, Mohamed, additional, Salama, Mohamed, additional, El-Jaafary, Shaimaa, additional, Hamed, Sharifa, additional, Tafesse Mengesha, Abenet, additional, Alemayehu Ayele, Biniyam, additional, Melka Oda, Dereje, additional, Zenebe Zewde, Yared, additional, Debebe Gelan, Yohanesse, additional, AkpaIu, Albert, additional, Charway-Felli, Augustina, additional, Stephen Sarfo, Fred, additional, Adjei, Patrick, additional, Obese, Vida, additional, Bocoum, Abdoulaye, additional, Koita, Abdou, additional, Oumar Guinto, Cheick, additional, Coulibaly, Toumany, additional, Maiga, Youssoufa, additional, Kone, Zaynab, additional, Bell, Abiodun, additional, Adebowale, Akintunde A., additional, Akpekpe, John, additional, lyagba, Alagoma, additional, Wulgo, Ali Mohammed, additional, Arabambi, Babawale, additional, Agu, Christian, additional, Dike, Franklin, additional, Ishola, Ismail, additional, Abiodun, Kehinde, additional, Ekenze, Oluchi, additional, Agabi Osigwe, Paul, additional, Balarabe, Salisu, additional, Abubakar, Sani, additional, Williams, Uduak, additional, Fall, Maouly, additional, Mamadou Diop, Alassane, additional, Hilaire Dominique, Ewodo Touna, additional, Mochan, Andre, additional, Modi, Girish, additional, Dindayal, Saiesha, additional, Ali Awadelkareem, Eman, additional, Dahawi, Maha, additional, Awadelkareem, Mosab Ali, additional, Misbah, Sarah, additional, Mushengez, Brighton, additional, Kimambo, Henrika, additional, Msango, Leonard, additional, Adebayo, Philip, additional, OKeng, Kigocha, additional, Diekker, Marieke, additional, URassa, Sarah, additional, Gouider, Riadh, additional, Ben Djebara, Mouna, additional, Gargouri, Amina, additional, Kacem, Imen, additional, Nasri, Amina, additional, Mrabet, Saloua, additional, Sghaier, Ikram, additional, Mkada, Imen, additional, Atadzhanov, Masharip, additional, Chishimba, Lorraine, additional, Rizig, Mie, additional, Jama, Fatumah, additional, Nalls, Mike, additional, Shamim, Ejaz, additional, Jonas, Cabell, additional, Williamson, Jared, additional, Hall, Deborah A., additional, Rosenbaum, Marc, additional, Davis, Staci, additional, Dean, Marissa, additional, Cromer, Candace, additional, Smith, Jenna, additional, Ruffrage, Lauren, additional, Richardson, Joseph, additional, Sipma, Rebeka, additional, Padmanaban, Manesh, additional, Warren, Natalie, additional, Mercado, Tomas, additional, Disbrow, Elizabeth, additional, Chauppeta, Brian, additional, Thomas-Dean, Fermine, additional, Toms, Jamie, additional, Lofton, Katelyn, additional, Rawls, Ashley, additional, Rizer, Kyle, additional, Black, Nieci, additional, Solle, Justin, additional, O'Grady, Alyssa, additional, Sherer, Todd, additional, Fiske, Brian, additional, Başak, A. Nazlı, additional, Tan, Ai Huey, additional, Noyce, Alastair, additional, Akpalu, Albert, additional, Espay, Alberto, additional, Martínez-Carrasco, Alejandro, additional, Medina, Alex, additional, Zimprich, Alexander, additional, Brice, Alexis, additional, Karimova, Altynay, additional, Hernandez, Alvaro, additional, Illarionova, Anastasia, additional, Quattrone, Andrea, additional, Singleton, Andrew B, additional, Sobering, Andrew K., additional, Vinuela, Angel, additional, Sanyaolu, Arinola, additional, Schumacher-Schuh, Artur F., additional, Kishore, Asha, additional, Ahmad-Annuar, Azlina, additional, Al Mubarak, Bashayer, additional, Tang, Beisha, additional, Pizarro Galleguillos, Benjamin, additional, Jeon, Beomseok, additional, Siddiqi, Bernadette, additional, Casey, Bradford, additional, Mollenhauer, Brit, additional, Carroll, Camille, additional, Rieder, Carlos, additional, Pantazis, Caroline B., additional, Comart, Charisse, additional, Lin, Chin-Hsien, additional, Klein, Christine, additional, Bale, Claire, additional, Shepherd, Claire E, additional, Wegel, Claire, additional, Martinez-Ramirez, Daniel, additional, Hall, Deborah, additional, Hernandez, Dena, additional, KP, Divya, additional, Nguyen, Duan, additional, Fon, Edward A., additional, Dadiotis, Efthymios, additional, Riley, Ekemini, additional, Iakovenko, Elena, additional, Stafford, Ellie, additional, Gatto, Emilia M, additional, Valente, Enza Maria, additional, Vollstedt, Eva-Juliane, additional, Faghri, Faraz, additional, Genc, Gencer, additional, Xiromerisiou, Georgia, additional, Hadjigorgiou, Georgios, additional, Hiu-Fai Chan, Germaine, additional, Arboleda, Gonzalo, additional, Kaishibayeva, Gulnaz, additional, Höglinger, Günter, additional, Leonard, Hampton, additional, Madoev, Harutyun, additional, Chen, Honglei, additional, Wu, Hsiu-Chuan, additional, Shang, Huifang, additional, F. Mata, Ignacio, additional, Keller Sarmiento, Ignacio Juan, additional, Dagklis, Ioannis, additional, Tarnanas, Ioannis, additional, Aasly, Jan O., additional, Hoenicka, Janet, additional, Corvol, Jean-Christophe, additional, Foo, Jia Nee, additional, Guo, Jifeng, additional, Junker, Johanna, additional, Carr, Jonathan, additional, Kim, Jonggeol Jeff, additional, Orozco, Jorge, additional, Jankovic, Joseph, additional, Shulman, Joshua, additional, Hunter, Julie, additional, Solle, Justin C., additional, Murphy, Kaileigh, additional, Nuytemans, Karen, additional, Kieburtz, Karl, additional, Lohmann, Katja, additional, Marek, Kenneth, additional, Mok, Kin Ying, additional, Kumar, Kishore, additional, Levine, Kristin, additional, Chahine, Lana M., additional, Lange, Lara M., additional, Pihlstrøm, Lasse, additional, Screven, Laurel, additional, Stefanis, Leonidas, additional, Shulman, Lisa, additional, Marsili, Luca, additional, Parnetti, Lucilla, additional, Kuhl, Maggie, additional, Funayama, Manabu, additional, Sharma, Manu, additional, Tan, Manuela, additional, Kauffman, Marcelo, additional, Miranda, Marcelo, additional, Bustamante, Maria Leonor, additional, Stamelou, Maria, additional, Periñan Tocino, Maria Teresa, additional, Cornejo-Olivas, Mario, additional, Jimenez del Rio, Marlene, additional, Koretsky, Mathew, additional, Rodriguez-Violante, Mayela, additional, Ellis, Melina, additional, Avenali, Micol, additional, Rentería, Miguel E., additional, Inca-Martines, Miguel z, additional, Nalls, Mike A., additional, Ibrahim Norlinah, Mohamed, additional, Umair, Muhammad, additional, Ip, Nancy, additional, Louie, Naomi, additional, Cheung, Nelson Yuk-Fai, additional, Mencacci, Niccolò Emanuele, additional, Wood, Nicholas, additional, Williams, Nigel, additional, Hattori, Nobutaka, additional, Abdul Murad, Nor Azian, additional, Ibrahim, Norlinah Mohamed, additional, Monchi, Oury, additional, Öztop Çakmak, Özgür, additional, Öztop Çakmak, Patricio Öztop Çakmak, additional, Lewis, Patrick Alfryn, additional, Pastor, Pau, additional, Reyes-Pérez, Paula, additional, Saffie Awad, Paula, additional, Chana, Pedro, additional, Chan, Phillip, additional, Kung, Pin-Jui, additional, Chan, Piu, additional, Pal, Pramod, additional, Lingappa Kukkle, Prashanth, additional, Ojha, Rajeev, additional, Kaiyrzhanov, Rauan, additional, Krüger, Rejko, additional, Amouri, Rim, additional, Weil, Rimona, additional, Rajan, Roopa, additional, Alcalay, Roy, additional, Wu, Ruey-Meei, additional, Borgohain, Rupam, additional, Sassi, Samia Ben, additional, Khachatryan, Samson, additional, El-Sadig, Sarah, additional, Wu, Serena, additional, Groppa, Sergio, additional, Azmin, Shahrul, additional, Lim, Shen-Yang, additional, Ur-Rehman, Shoaib, additional, Ertan, Sibel, additional, Stott, Simon, additional, Jasaitye, Simona, additional, Chowdhury, Sohini, additional, Dumanis, Sonya, additional, Bardien, Soraya, additional, Lubbe, Steven, additional, Koks, Sulev, additional, Dey, Sumit, additional, Foroud, Tatiana, additional, Fon, Ted, additional, Beach, Thomas, additional, Gasser, Thomas, additional, Anderson, Tim, additional, Nguyen, Toan, additional, Schirinzi, Tommaso, additional, Shiraishi, Tomotaka, additional, Pitcher, Toni, additional, Tumas, Vitor, additional, Mohamed, Wael, additional, Kamel, Walaa A., additional, Luo, Wei, additional, Zhou, Xiaopu, additional, Zewde, Yared Z., additional, Song, Yeajin, additional, Wen, Yi, additional, Wu, Yihru, additional, Joong Kim, Yun, additional, and Tavadyan, Zaruhi, additional

Published
2023
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24. Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Author

Sugier, Pierre-Emmanuel, Lucotte, Elise A., Domenighetti, Cloé, Law, Matthew H., Iles, Mark M., Brown, Kevin, Amos, Christopher, McKay, James D., Hung, Rayjean J., Karimi, Mojgan, Bacq-Daian, Delphine, Boland-Augé, Anne, Olaso, Robert, Deleuze, Jean-François, Lesueur, Fabienne, Ostroumova, Evgenia, Kesminiene, Ausrele, de Vathaire, Florent, Guénel, Pascal, consortium, The Epithyr, Sreelatha, Ashwin Ashok Kumar, Schulte, Claudia, Grover, Sandeep, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimios, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Nakayama, Akiyoshi, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Guedes, Leonor Correia, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy, Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Rödström, Emil Ygland, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Landoulsi, Zied, consortium, Courage-PD, Truong, Thérèse, Elbaz, Ales, JPND Courage-PD [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], and Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center]

Subjects
Male, Lung Neoplasms, Parkinson's disease, Neurology [D14] [Human health sciences], RESEARCH ARTICLES, RESEARCH ARTICLE, SDG 3 - Good Health and Well-being, genetics [Parkinson Disease], Risk Factors, pleiotropy, Humans, cancer, ddc:610, genetics [Genetic Predisposition to Disease], Ovarian Neoplasms, Neurologie [D14] [Sciences de la santé humaine], Prostatic Neoplasms, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], genetic correlation, parkinson's disease, polygenic risk score, epidemiology [Melanoma], Neurology, genetics [Melanoma], genetics [Polymorphism, Single Nucleotide], Female, epidemiology [Parkinson Disease], Genetics & genetic processes [F10] [Life sciences], Neurology (clinical), Génétique & processus génétiques [F10] [Sciences du vivant], Genome-Wide Association Study
Abstract

BackgroundEpidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties.ObjectiveWe used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors.MethodsWe used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses.ResultsWe confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31).ConclusionsWe show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Published
2023

25. Genetic meta-analysis of levodopa induced dyskinesia in Parkinson′s disease

Author

Martinez, Alejandro, primary, Real, Raquel, additional, Lawton, Michael, additional, Iwaki, Hirotaka, additional, Tan, Manuela, additional, Wu, Lesley, additional, Williams, Nigel, additional, Carroll, Camille, additional, Grosset, Donald, additional, Hardy, John, additional, Ryten, Mina, additional, Foltynie, Thomas, additional, Ben-Shlomo, Yoav, additional, Shoai, Maryam, additional, and Morris, Huw, additional

Published
2023
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26. Lysosomal polygenic risk is associated with the severity of neuropathology in Lewy body disease

Author

Tunold, Jon-Anders, primary, Tan, Manuela M X, additional, Koga, Shunsuke, additional, Geut, Hanneke, additional, Rozemuller, Annemieke J M, additional, Valentino, Rebecca, additional, Sekiya, Hiroaki, additional, Martin, Nicholas B, additional, Heckman, Michael G, additional, Bras, Jose, additional, Guerreiro, Rita, additional, Dickson, Dennis W, additional, Toft, Mathias, additional, van de Berg, Wilma, additional, Ross, Owen A, additional, and Pihlstrøm, Lasse, additional

Published
2023
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28. Analysis of DNM3 and VAMP4 as genetic modifiers of LRRK2 Parkinson’s disease

Author

Brown, Emmeline E., Blauwendraat, Cornelis, Trinh, Joanne, Rizig, Mie, Nalls, Mike A., Leveille, Etienne, Ruskey, Jennifer A., Jonvik, Hallgeir, Tan, Manuela M.X., Bandres-Ciga, Sara, Hassin-Baer, Sharon, Brockmann, Kathrin, Infante, Jon, Tolosa, Eduardo, Ezquerra, Mario, Ben Romdhan, Sawssan, Benmahdjoub, Mustapha, Arezki, Mohamed, Mhiri, Chokri, Hardy, John, Singleton, Andrew B., Alcalay, Roy N., Gasser, Thomas, Grosset, Donald G., Williams, Nigel M., Pittman, Alan, Gan-Or, Ziv, Fernandez-Santiago, Ruben, Brice, Alexis, Lesage, Suzanne, Farrer, Matthew, Wood, Nicholas, and Morris, Huw R.

Published
2021
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29. Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], JPND Courage-PD [sponsor], Sugier, Pierre-Emmanuel, Lucotte, Elise A., Domenighetti, Cloé, Law, Matthew H., Iles, Mark M., Brown, Kevin, Amos, Christopher, McKay, James D., Hung, Rayjean J., Karimi, Mojgan, Bacq-Daian, Delphine, Boland-Augé, Anne, Olaso, Robert, Deleuze, Jean-François, Lesueur, Fabienne, Ostroumova, Evgenia, Kesminiene, Ausrele, de Vathaire, Florent, Guénel, Pascal, consortium, The Epithyr, Sreelatha, Ashwin Ashok Kumar, Schulte, Claudia, Grover, Sandeep, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimios, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Nakayama, Akiyoshi, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Guedes, Leonor Correia, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy, Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Rödström, Emil Ygland, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Landoulsi, Zied, consortium, Courage-PD, Truong, Thérèse, Elbaz, Ales, Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], JPND Courage-PD [sponsor], Sugier, Pierre-Emmanuel, Lucotte, Elise A., Domenighetti, Cloé, Law, Matthew H., Iles, Mark M., Brown, Kevin, Amos, Christopher, McKay, James D., Hung, Rayjean J., Karimi, Mojgan, Bacq-Daian, Delphine, Boland-Augé, Anne, Olaso, Robert, Deleuze, Jean-François, Lesueur, Fabienne, Ostroumova, Evgenia, Kesminiene, Ausrele, de Vathaire, Florent, Guénel, Pascal, consortium, The Epithyr, Sreelatha, Ashwin Ashok Kumar, Schulte, Claudia, Grover, Sandeep, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimios, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Nakayama, Akiyoshi, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Guedes, Leonor Correia, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy, Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Rödström, Emil Ygland, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Landoulsi, Zied, consortium, Courage-PD, Truong, Thérèse, and Elbaz, Ales

Abstract

Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly dri

Published
2023

30. Defining the causes of sporadic Parkinson’s disease in the global Parkinson’s genetics program (GP2)

Author

National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), Periñán, María Teresa, National Institute on Aging (US), National Institutes of Health (US), Aligning Science Against Parkinson's, Parkinson Research Foundation, Department of Health and Human Services (US), Towns, Clodagh, Richer, Madeleine, Jasaityte, Simona, Stafford, Eleanor J., Joubert, Julie, Antar, Tarek, Martínez-Carrasco, Alejandro, Makarious, Mary B., Casey, Bradford, Vitale, Dan, Levine, Kristin, Leonard, Hampton, Pantazis, Caroline B., Screven, Laurel A., Hernández, Dena G., Wegel, Claire E., Solle, Justin, Nalls, Mike A., Blauwendraat, Cornelis, Singleton, Andrew B., Tan, Manuela M. X., Iwaki, Hirotaka, Morris, Huw, Global Parkinson’s Genetics Program (GP2), and Periñán, María Teresa

Abstract

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia.

Published
2023

31. Genetics of validated Parkinson's disease subtypes in the Oxford Discovery and Tracking Parkinson's cohorts

Author

Lawton, Michael, Tan, Manuela Mx, Ben-Shlomo, Yoav, Baig, Fahd, Barber, Thomas, Klein, Johannes C, Evetts, Samuel G, Millin, Stephanie, Malek, Naveed, Grosset, Katherine, Barker, Roger A, Williams, Nigel, Burn, David J, Foltynie, Thomas, Morris, Huw R, Wood, Nicholas, Grosset, Donald G, Hu, Michele Tao-Ming, Lawton, Michael [0000-0002-3419-0354], Tan, Manuela Mx [0000-0001-5835-669X], Klein, Johannes C [0000-0002-8553-2801], Foltynie, Thomas [0000-0003-0752-1813], Morris, Huw R [0000-0002-5473-3774], Hu, Michele Tao-Ming [0000-0001-6382-5841], and Apollo - University of Cambridge Repository

Subjects
GENETICS, PARKINSON'S DISEASE
Abstract

OBJECTIVES: To explore the genetics of four Parkinson's disease (PD) subtypes that have been previously described in two large cohorts of patients with recently diagnosed PD. These subtypes came from a data-driven cluster analysis of phenotypic variables. METHODS: We looked at the frequency of genetic mutations in glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 against our subtypes. Then we calculated Genetic Risk Scores (GRS) for PD, multiple system atrophy, progressive supranuclear palsy, Lewy body dementia, and Alzheimer's disease. These GRSs were regressed against the probability of belonging to a subtype in the two independent cohorts and we calculated q-values as an adjustment for multiple testing across four subtypes. We also carried out a Genome-Wide Association Study (GWAS) of belonging to a subtype. RESULTS: A severe disease subtype had the highest rates of patients carrying GBA mutations while the mild disease subtype had the lowest rates (p=0.009). Using the GRS, we found a severe disease subtype had a reduced genetic risk of PD (p=0.004 and q=0.015). In our GWAS no individual variants met genome wide significance (

Published
2022

32. Combining biomarkers for prognostic modelling of Parkinson's disease

Author

Vijiaratnam, Nirosen, Lawton, Michael, Heslegrave, Amanda J, Guo, Tong, Tan, Manuela, Jabbari, Edwin, Real, Raquel, Woodside, John, Grosset, Katherine, Chelban, Viorica, Athauda, Dilan, Girges, Christine, Barker, Roger A, Hardy, John, Wood, Nicholas, Houlden, Henry, Williams, Nigel, Ben-Shlomo, Yoav, Zetterberg, Henrik, Grosset, Donald G, Foltynie, Thomas, Morris, Huw R, PRoBaND Clinical Consortium, Vijiaratnam, Nirosen [0000-0002-9671-0212], Lawton, Michael [0000-0002-3419-0354], Heslegrave, Amanda J [0000-0002-7290-6405], Guo, Tong [0000-0001-9395-3617], Tan, Manuela [0000-0001-5835-669X], Jabbari, Edwin [0000-0001-6844-882X], Real, Raquel [0000-0001-8117-742X], Chelban, Viorica [0000-0002-5817-6290], Athauda, Dilan [0000-0001-8594-2483], Girges, Christine [0000-0001-5019-6812], Barker, Roger A [0000-0001-8843-7730], Houlden, Henry [0000-0002-2866-7777], Williams, Nigel [0000-0003-1177-6931], Ben-Shlomo, Yoav [0000-0001-6648-3007], Zetterberg, Henrik [0000-0002-4671-6763], Grosset, Donald G [0000-0002-2757-8203], Foltynie, Thomas [0000-0003-0752-1813], Morris, Huw R [0000-0002-5473-3774], and Apollo - University of Cambridge Repository

Subjects
parkinson's disease
Abstract

BACKGROUND: Patients with Parkinson's disease (PD) have variable rates of progression. More accurate prediction of progression could improve selection for clinical trials. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be further improved by blood biomarkers. OBJECTIVE: To determine if blood biomarkers (serum neurofilament light (NfL) and genetic status (glucocerebrosidase, GBA and apolipoprotein E (APOE))) are useful in addition to clinical measures for prognostic modelling in PD. METHODS: We evaluated the relationship between serum NfL and baseline and longitudinal clinical measures as well as patients' genetic (GBA and APOE) status. We classified patients as having a favourable or an unfavourable outcome based on a previously validated model, and explored how blood biomarkers compared with clinical variables in distinguishing prognostic phenotypes . RESULTS: 291 patients were assessed in this study. Baseline serum NfL was associated with baseline cognitive status. Nfl predicted a shorter time to dementia, postural instability and death (dementia-HR 2.64; postural instability-HR 1.32; mortality-HR 1.89) whereas APOEe4 status was associated with progression to dementia (dementia-HR 3.12, 95% CI 1.63 to 6.00). NfL levels and genetic variables predicted unfavourable progression to a similar extent as clinical predictors. The combination of clinical, NfL and genetic data produced a stronger prediction of unfavourable outcomes compared with age and gender (area under the curve: 0.74-age/gender vs 0.84-ALL p=0.0103). CONCLUSIONS: Clinical trials of disease-modifying therapies might usefully stratify patients using clinical, genetic and NfL status at the time of recruitment.

Published
2022
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33. Dissecting the limited genetic overlap of Parkinson's and Alzheimer's disease

Author

Andersen, Maren Stolp, Tan, Manuela, Holtman, Inge R., Hardy, John, Pihlstrøm, Lasse, and Molecular Neuroscience and Ageing Research (MOLAR)

Subjects
Neurons, INSIGHTS, Alzheimer Disease, IMPACT, General Neuroscience, Humans, Parkinson Disease, Microglia, Neurology (clinical), GENOME-WIDE ASSOCIATION, RISK LOCI, Genome-Wide Association Study
Abstract

Parkinson's disease and Alzheimer's disease show overlapping features both clinically and neuropathologically and elucidating shared mechanisms could have important implications for therapeutic strategies. Evidence for genetic overlap is limited, although enrichment of heritability in genomic regions relevant to microglia has been demonstrated in both disorders. Using summary statistics from genome-wide association studies, we assessed genetic covariance stratified by cell types and local genetic correlation between Parkinson's and Alzheimer's disease. Significant covariance was observed for neurons only (p = 0.00046), and local genetic correlation was significant only in the human leukocyte antigen region (p = 1.0e-05). Our findings support a minor genetic overlap between these two disorders.

Published
2022

34. Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia

Author

Real, Raquel, primary, Martinez-Carrasco, Alejandro, additional, Reynolds, Regina H, additional, Lawton, Michael A, additional, Tan, Manuela M X, additional, Shoai, Maryam, additional, Corvol, Jean-Christophe, additional, Ryten, Mina, additional, Bresner, Catherine, additional, Hubbard, Leon, additional, Brice, Alexis, additional, Lesage, Suzanne, additional, Faouzi, Johann, additional, Elbaz, Alexis, additional, Artaud, Fanny, additional, Williams, Nigel, additional, Hu, Michele T M, additional, Ben-Shlomo, Yoav, additional, Grosset, Donald G, additional, Hardy, John, additional, and Morris, Huw R, additional

Published
2022
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35. Association of genetic variation at the GJA5/ACP6 locus with motor progression in Parkinson’s

Author

Martinez-Carrasco, Alejandro, primary, Real, Raquel, additional, Lawton, Michael, additional, Reynolds, Regina H, additional, Tan, Manuela M. X., additional, Wu, Lesley, additional, Williams, Nigel M., additional, Carroll, Camille, additional, Corvol, Jean-Christophe, additional, Hu, Michele T.M., additional, Grosset, Donald G., additional, Hardy, John, additional, Ryten, Mina, additional, Ben-Shlomo, Yoav, additional, Shoai, Maryam, additional, and Morris, Huw R., additional

Published
2022
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36. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author

Leonard, Hampton L, Murtadha, Ruqaya, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P, Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Martinez-Carrasco, Alejandro, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M X, Jama, Alina, Periñán, María Teresa, Makarious, Mary B, Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R, Alvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Müller-Nedebock, Amica Corda, Real, Raquel, Reynolds, Regina H, Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C, Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J, Song, Yeajin, Gil-Martinez, Ana-Luisa, Singleton, Andrew, Nalls, Mike A, Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair J, Program, The Global Parkinson’s Genetics, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I, Jadhav, Bharati, and Consortium, International Parkinson Disease Genomics

Subjects
Cellular and Molecular Neuroscience, Neurology, Neurology (clinical), ddc:610
Abstract

Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.

Published
2023

37. Author Correction: The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson's disease data

Author

Leonard, Hampton L, Murtadha, Ruqaya, Huxford, Brook, Storm, Catherine, Towns, Clodagh, Vitale, Dan, Chetty, Devina, Yu, Eric, Grenn, Francis P, Salazar, Gabriela, Rateau, Geoffrey, Iwaki, Hirotaka, Martinez-Carrasco, Alejandro, Elsayed, Inas, Foote, Isabelle Francesca, Jansen van Rensburg, Zuné, Kim, Jonggeol Jeff, Yuan, Jie, Lake, Julie, Brolin, Kajsa, Senkevich, Konstantin, Wu, Lesley, Tan, Manuela M X, Jama, Alina, Periñán, María Teresa, Makarious, Mary B, Ta, Michael, Pillay, Nikita Simone, Betancor, Oswaldo Lorenzo, Reyes-Pérez, Paula R, Alvarez Jerez, Pilar, Saini, Prabhjyot, Al-Ouran, Rami, Sivakumar, Ramiya, Müller-Nedebock, Amica Corda, Real, Raquel, Reynolds, Regina H, Hu, Ruifneg, Abrahams, Shameemah, Rao, Shilpa C, Antar, Tarek, Leal, Thiago Peixoto, Iankova, Vassilena, Scotton, William J, Song, Yeajin, Gil-Martinez, Ana-Luisa, Singleton, Andrew, Nalls, Mike A, Dey, Sumit, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Noyce, Alastair J, Program, The Global Parkinson’s Genetics, Illarionova, Anastasia, Moore, Anni, Bustos, Bernabe I, Jadhav, Bharati, and Consortium, International Parkinson Disease Genomics

Subjects
ddc:610
Published
2023

38. Genome-wide Association and Meta-analysis of Age at Onset in Parkinson Disease: Evidence From the COURAGE-PD Consortium

Author

Grover, Sandeep, Kumar Sreelatha, Ashwin Ashok, Landoulsi, Zied, May, Patrick, Bobbili, Dheeraj, Edsall, Connor, Bartusch, Felix, Hanussek, Maximilian, Krüger, Jens, Hernandez, Dena G, Blauwendraat, Cornelis, Mellick, George D, Pihlstrom, Lasse, Zimprich, Alexander, Pirker, Walter, Tan, Manuela, Rogaeva, Ekaterina, Lang, Anthony, Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Domenighetti, Cloé, Chartier-Harlin, Marie-Christine, Mutez, Eugenie, Brockmann, Kathrin, Deutschländer, Angela B, Hadjigeorgiou, Georges M, Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Schulte, Claudia, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Burbulla, Lena F, Matsuo, Hirotaka, Sugier, Pierre-Emmanuel, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Pavelka, Lukas, van de Warrenburg, Bart P C, Bloem, Bastiaan R, Singleton, Andrew B, Aasly, Jan, Radivojkov-Blagojevic, Milena, Toft, Mathias, Guedes, Leonor Correia, Ferreira, Joaquim J, Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Lichtner, Peter, Pedersen, Nancy L, Ran, Caroline, Belin, Andrea C, Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E, Morrison, Karen E, Krainc, Dimitri, Farrer, Matt J, Kruger, Rejko, Mohamed, Océane, Elbaz, Alexis, Gasser, Thomas, Sharma, Manu, Genetics, and the Comprehensive Unbiased Risk Factor Assessment for, Disease, Environment in Parkinson's, Portugal, Berta, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique Neurosciences [CHU Pitié Salpêtrière] (CIC Neurosciences), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Lille Neurosciences & Cognition - U 1172 (LilNCog), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), FOR2488, INTER/DFG/17/11583046, INTER/DFG/19/14429377, Michael J. Fox Foundation for Parkinson's Research, MJFF, EU Joint Programme – Neurodegenerative Disease Research, JPND: 01ED1406, Multiple System Atrophy Coalition, MSA, European Commission, EC: EP1802749, Deutsche Forschungsgemeinschaft, DFG: DFG/SH 599/6-1, Fonds National de la Recherche Luxembourg, FNR: FNR/P13/6682797, Bundesministerium für Bildung und Forschung, BMBF, Université Paris-Saclay, The COURAGE-PD Consortium is conducted under a partnership agreement between 35 studies. The COURAGE-PD Consortium is supported by the EU Joint Program for Neurodegenerative Disease Research (JPND, neurodegenerationresearch.eu/initiatives/annual-calls-for-proposals/closed-calls/risk-factors-2012/risk-factor-call-results/courage-pd/ , Grant ID: 01ED1406)., and The Article Processing Charge was funded by the authors.

Subjects
parkinson’s disease, [SDV]Life Sciences [q-bio], burden of disease, Polymorphism, Single Nucleotide, Duration of disease, genetic heritability, duration of disease, genetics [Parkinson Disease], age at onset, Humans, Genetic Predisposition to Disease, ddc:610, Age of Onset, genetics [Genetic Predisposition to Disease], Burden of disease, Age at onset, Parkinson Disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Courage, Parkinson’s disease, Genetic heritability, Female, Neurology (clinical), epidemiology [Parkinson Disease], Genome-Wide Association Study
Abstract

Background and ObjectivesConsiderable heterogeneity exists in the literature concerning genetic determinants of the age at onset (AAO) of Parkinson disease (PD), which could be attributed to a lack of well-powered replication cohorts. The previous largest genome-wide association studies (GWAS) identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on the AAO of PD; these have not been independently replicated. This study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations.MethodsA meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease (COURAGE-PD) Consortium. This was followed by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson Disease Genomics Consortium (IPDGC).ResultsThe COURAGE-PD Consortium included a cohort of 8,535 patients with PD (91.9%: Europeans and 9.1%: East Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD = 11.6), with an underrepresentation of females (40.2%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE = 0.057). None of the loci reached genome-wide significance (p < 5 × 10−8). Nevertheless, the COURAGE-PD dataset confirmed the role of the previously published TMEM175 variant as a genetic determinant of the AAO of PD with Bonferroni-corrected nominal levels of significance (p < 0.025): (rs34311866: β(SE)COURAGE = 0.477(0.203), pCOURAGE = 0.0185). The subsequent meta-analysis of COURAGE-PD and IPDGC datasets (Ntotal = 25,950) led to the identification of 2 genome-wide significant association signals on Chr 4, including the previously reported SNCA locus (rs983361: β(SE)COURAGE+IPDGC = 0.720(0.122), pCOURAGE+IPDGC = 3.13 × 10−9) and a novel BST1 locus (rs4698412: β(SE)COURAGE+IPDGC = −0.526(0.096), pCOURAGE+IPDGC = 4.41 × 10−8).DiscussionOur study further refines the genetic architecture of Chr 4 underlying the AAO of the PD phenotype through the identification of BST1 as a novel AAO PD locus. These findings open a new direction for the development of treatments to delay the onset of PD.

Published
2022

42. Association between the LRP1B and APOE loci in the development of Parkinson's disease dementia.

Author

Real, Raquel, Martinez-Carrasco, Alejandro, Reynolds, Regina H, Lawton, Michael A, Tan, Manuela M X, Shoai, Maryam, Corvol, Jean-Christophe, Ryten, Mina, Bresner, Catherine, Hubbard, Leon, Brice, Alexis, Lesage, Suzanne, Faouzi, Johann, Elbaz, Alexis, Artaud, Fanny, Williams, Nigel, Hu, Michele T M, Ben-Shlomo, Yoav, Grosset, Donald G, and Hardy, John

Subjects
PARKINSON'S disease, MOVEMENT disorders, DEMENTIA, APOLIPOPROTEIN E, LOCUS (Genetics), COGNITION disorders
Abstract

Parkinson's disease is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of Parkinson's disease, particularly in the later stages of the disease. However, the rate of cognitive decline varies among Parkinson's disease patients, and the genetic basis for this heterogeneity is incompletely understood. To explore the genetic factors associated with rate of progression to Parkinson's disease dementia, we performed a genome-wide survival meta-analysis of 3,923 clinically diagnosed Parkinson's disease cases of European ancestry from four longitudinal cohorts. In total, 6.7% of individuals with Parkinson's disease developed dementia during study follow-up, on average 4.4 ± 2.4 years from disease diagnosis. We have identified the APOE ε4 allele as a major risk factor for the conversion to Parkinson's disease dementia [hazards ratio = 2.41 (1.94-3.00), P = 2.32 × 10-15], as well as a new locus within the ApoE and APP receptor LRP1B gene [hazards ratio = 3.23 (2.17-4.81), P = 7.07 × 10-09]. In a candidate gene analysis, GBA variants were also identified to be associated with higher risk of progression to dementia [hazards ratio = 2.02 (1.21-3.32), P = 0.007]. CSF biomarker analysis also implicated the amyloid pathway in Parkinson's disease dementia, with significantly reduced levels of amyloid β42 (P = 0.0012) in Parkinson's disease dementia compared to Parkinson's disease without dementia. These results identify a new candidate gene associated with faster conversion to dementia in Parkinson's disease and suggest that amyloid-targeting therapy may have a role in preventing Parkinson's disease dementia. [ABSTRACT FROM AUTHOR]

Published
2023
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43. Genome-wide Association and Meta-analysis of Age-at-Onset in Parkinson Disease: Evidence From COURAGE-PD Consortium 10.1212/WNL.0000000000200699

Author

Grover, Sandeep, Ashwin, Ashok Kumar Sreelatha, Pihlstrom, Lasse, Domenighetti, Cloé, Schulte, Claudia, Sugier, Pierre-Emmanuel, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Mohamed, Océane, Portugal, Berta, Landoulsi, Zied, May, Patrick, Bobbili, Dheeraj Reddy, Edsall, Connor, Bartusch, Felix, Hanussek, Maximilian, Krüger, Jens, Hernandez, Dena G., Blauwendraat, Cornelis, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Tan, Manuela, Rogaeva, Ekaterina, Lang, Anthony, Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugenie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Burbulla, Lena F., Matsuo, Hirotaka, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Pavelka, Lukas, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Singleton, Andrew B., Aasly, Jan, Toft, Mathias, Guedes, Leonor Correia, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E., Morrison, Karen E., Krainc, Dimitri, Farrer, Matt J., Krüger, Rejko, Elbaz, Alexis, Gasser, Thomas, Sharma, Manu, of, On Behalf, Genetics, The Comprehensive Unbiased Risk Factor Assessment For, consortium, Environment In Parkinson Textquoterights Disease Courage-P. D., Fonds National de la Recherche - FnR [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], and Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center]

Subjects
Neurologie [D14] [Sciences de la santé humaine], Parkinson's disease, Neurology [D14] [Human health sciences], Age of onset, GWAS, Genetics & genetic processes [F10] [Life sciences], Génétique & processus génétiques [F10] [Sciences du vivant]
Abstract

Background and Objectives: Considerable heterogeneity exists in the literature concerning genetic determinants of the age of onset (AAO) of Parkinson\textquoterights disease (PD), which could be attributed to lack of well-powered replication cohorts. The previous largest GWAS identified SNCA and TMEM175 loci on chromosome (Chr) 4 with a significant influence on AAO of PD, these have not been independently replicated. The present study aims to conduct a meta-analysis of GWAS of PD AAO and validate previously observed findings in worldwide populations.Methods: A meta-analysis was performed on PD AAO GWAS of 30 populations of predominantly European ancestry from the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson\textquoterights Disease (COURAGE-PD) consortium. This was followed up by combining our study with the largest publicly available European ancestry dataset compiled by the International Parkinson disease Genomics Consortium (IPDGC).Results: The COURAGE-PD included a cohort of 8,535 patients with PD (91.9\%: Europeans, 9.1\%: East-Asians). The average AAO in the COURAGE-PD dataset was 58.9 years (SD=11.6), with an under-representation of females (40.2\%). The heritability estimate for AAO in COURAGE-PD was 0.083 (SE=0.057). None of the loci reached genome-wide significance (P\

Published
2022

44. The Interaction between HLA-DRB1 and Smoking in Parkinson's Disease Revisited

Author

Domenighetti, Cloé, Douillard, Venceslas, Sugier, Pierre-Emmanuel, Sreelatha, Ashwin Ashok Kumar, Schulte, Claudia, Grover, Sandeep, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Gourraud, Pierre-Antoine, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Duga, Stefano, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Nakayama, Akiyoshi, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Correia Guedes, Leonor, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Ygland Rödström, Emil, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, KraincMD, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Vince, Nicolas, Elbaz, Alexis, Genetics, Comprehensive Unbiased Risk Factor Assessment For, Consortium, Environment In Parkinson S Disease Courage-P. D., Fonds National de la Recherche - FnR [sponsor], Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], and Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center]

Subjects
Neurologie [D14] [Sciences de la santé humaine], genetics [HLA-DRB1 Chains], Neurology [D14] [Human health sciences], Parkinson's disease, Smoking, Parkinson Disease, genetics [Smoking], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Polymorphism, Single Nucleotide, smoking, gene-environment interaction, HLA, Neurology, genetics [Parkinson Disease], genetics [Polymorphism, Single Nucleotide], Humans, Genetic Predisposition to Disease, ddc:610, Genetics & genetic processes [F10] [Life sciences], Neurology (clinical), Génétique & processus génétiques [F10] [Sciences du vivant], HLA-DRB1 Chains
Abstract

Contains fulltext : 282469.pdf (Publisher’s version ) (Open Access) BACKGROUND: Two studies that examined the interaction between HLA-DRB1 and smoking in Parkinson's disease (PD) yielded findings in opposite directions. OBJECTIVE: To perform a large-scale independent replication of the HLA-DRB1 × smoking interaction. METHODS: We genotyped 182 single nucleotide polymorphism (SNPs) associated with smoking initiation in 12 424 cases and 9480 controls to perform a Mendelian randomization (MR) analysis in strata defined by HLA-DRB1. RESULTS: At the amino acid level, a valine at position 11 (V11) in HLA-DRB1 displayed the strongest association with PD. MR showed an inverse association between genetically predicted smoking initiation and PD only in absence of V11 (odds ratio, 0.74, 95% confidence interval, 0.59-0.93, P(Interaction) = 0.028). In silico predictions of the influence of V11 and smoking-induced modifications of α-synuclein on binding affinity showed findings consistent with this interaction pattern. CONCLUSIONS: Despite being one of the most robust findings in PD research, the mechanisms underlying the inverse association between smoking and PD remain unknown. Our findings may help better understand this association. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Published
2022

45. Genome-wide determinants of mortality and motor progression in Parkinson’s disease

Author

Tan, Manuela MX, primary, Lawton, Michael A, additional, Pollard, Miriam I, additional, Brown, Emmeline, additional, Real, Raquel, additional, Martinez Carrasco, Alejandro, additional, Bekadar, Samir, additional, Jabbari, Edwin, additional, Reynolds, Regina H, additional, Iwaki, Hirotaka, additional, Blauwendraat, Cornelis, additional, Kanavou, Sofia, additional, Hubbard, Leon, additional, Malek, Naveed, additional, Grosset, Katherine A, additional, Bajaj, Nin, additional, Barker, Roger A, additional, Burn, David J, additional, Bresner, Catherine, additional, Foltynie, Thomas, additional, Wood, Nicholas W, additional, Williams-Gray, Caroline H, additional, Andreassen, Ole A, additional, Toft, Mathias, additional, Elbaz, Alexis, additional, Artaud, Fanny, additional, Brice, Alexis, additional, Corvol, Jean-Christophe, additional, Aasly, Jan, additional, Farrer, Matthew J, additional, Nalls, Michael A, additional, Singleton, Andrew B, additional, Williams, Nigel M, additional, Ben-Shlomo, Yoav, additional, Hardy, John, additional, Hu, Michele TM, additional, Grosset, Donald G, additional, Shoai, Maryam, additional, Pihlstrøm, Lasse, additional, and Morris, Huw R, additional

Published
2022
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46. Genetics of validated Parkinson’s disease subtypes in the Oxford Discovery and Tracking Parkinson’s cohorts

Author

Lawton, Michael, primary, Tan, Manuela MX, additional, Ben-Shlomo, Yoav, additional, Baig, Fahd, additional, Barber, Thomas, additional, Klein, Johannes C, additional, Evetts, Samuel G, additional, Millin, Stephanie, additional, Malek, Naveed, additional, Grosset, Katherine, additional, Barker, Roger A, additional, Williams, Nigel, additional, Burn, David J, additional, Foltynie, Thomas, additional, Morris, Huw R, additional, Wood, Nicholas, additional, Grosset, Donald G, additional, and Hu, Michele Tao-Ming, additional

Published
2022
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47. Association between the LRP1B and APOEloci and the development of Parkinson's disease dementia

Author

Real, Raquel, primary, Martinez-Carrasco, Alejandro, additional, Reynolds, Regina H., additional, Lawton, Michael A., additional, Tan, Manuela M. X., additional, Shoai, Maryam, additional, Corvol, Jean-Christophe, additional, Ryten, Mina, additional, Bresner, Catherine, additional, Hubbard, Leon, additional, Brice, Alexis, additional, Lesage, Suzanne, additional, Faouzi, Johann, additional, Elbaz, Alexis, additional, Artaud, Fanny, additional, Williams, Nigel, additional, Hu, Michele T. M., additional, Ben-Shlomo, Yoav, additional, Grosset, Donald G., additional, Hardy, John, additional, and Morris, Huw R., additional

Published
2022
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48. Combining biomarkers for prognostic modelling of Parkinson’s disease

Author

Vijiaratnam, Nirosen, primary, Lawton, Michael, additional, Heslegrave, Amanda J, additional, Guo, Tong, additional, Tan, Manuela, additional, Jabbari, Edwin, additional, Real, Raquel, additional, Woodside, John, additional, Grosset, Katherine, additional, Chelban, Viorica, additional, Athauda, Dilan, additional, Girges, Christine, additional, Barker, Roger A, additional, Hardy, John, additional, Wood, Nicholas, additional, Houlden, Henry, additional, Williams, Nigel, additional, Ben-Shlomo, Yoav, additional, Zetterberg, Henrik, additional, Grosset, Donald G, additional, Foltynie, Thomas, additional, and Morris, Huw R, additional

Published
2022
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49. The IPDGC/GP2 Hackathon - an open science event for training in data science, genomics, and collaboration using Parkinson’s disease data

Author

Leonard, Hampton L., primary, Murtadha, Ruqaya, additional, Martinez-Carrasco, Alejandro, additional, Muller-Nedebock, Amica, additional, Gil-Martinez, Ana-Luisa, additional, Illarionova, Anastasia, additional, Moore, Anni, additional, Bustos, Bernabe I., additional, Jadhav, Bharati, additional, Huxford, Brook, additional, Storm, Catherine, additional, Towns, Clodagh, additional, Vitale, Dan, additional, Chetty, Devina, additional, Yu, Eric, additional, Jama, Fatumah, additional, Grenn, Francis P., additional, Salazar, Gabriela, additional, Rateau, Geoffrey, additional, Iwaki, Hirotaka, additional, Elsayed, Inas, additional, Foote, Isabelle, additional, van Rensburg, Zuné Jansen, additional, Kim, Jonggeol Jeff, additional, Yuan, Jie, additional, Lake, Julie, additional, Brolin, Kajsa, additional, Senkevich, Konstantin, additional, Wu, Lesley, additional, Tan, Manuela M.X., additional, Periñán, María Teresa, additional, Makarious, Mary B, additional, Ta, Michael, additional, Pillay, Nikita Simone, additional, Betancor, Oswaldo Lorenzo, additional, Reyes-Pérez, Paula R., additional, Jerez, Pilar Alvarez, additional, Saini, Prabhjyot, additional, al-Ouran, Rami, additional, Sivakumar, Ramiya, additional, Real, Raquel, additional, Reynolds, Regina H., additional, Hu, Ruifneg, additional, Abrahams, Shameemah, additional, Rao, Shilpa C., additional, Antar, Tarek, additional, Leal, Thiago Peixoto, additional, Iankova, Vassilena, additional, Scotton, William J., additional, Song, Yeajin, additional, Singleton, Andrew, additional, Nalls, Mike A., additional, Dey, Sumit, additional, Bandres-Ciga, Sara, additional, Blauwendraat, Cornelis, additional, and Noyce, Alastair J., additional

Published
2022
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50. Dairy Intake and Parkinson's Disease: A Mendelian Randomization Study

Author

Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Fonds National de la Recherche - FnR [sponsor], JPND Courage-PD [sponsor], Domenighetti, Cloé, Sugier, Pierre-Emmanuel, Ashok Kumar Sreelatha, Ashwin, Schulte, Claudia, Grover, Sandeep, Mohamed, Océane, Portugal, Berta, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Duga, Stefano, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Correia Guedes, Leonor, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Elbaz, Alexis, Genetics, The Comprehensive Unbiased Risk Factor Assessment For, Consortium, Environment In Parkinson S Disease Courage-P. D., Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center], Luxembourg Centre for Systems Biomedicine (LCSB): Clinical & Experimental Neuroscience (Krüger Group) [research center], Fonds National de la Recherche - FnR [sponsor], JPND Courage-PD [sponsor], Domenighetti, Cloé, Sugier, Pierre-Emmanuel, Ashok Kumar Sreelatha, Ashwin, Schulte, Claudia, Grover, Sandeep, Mohamed, Océane, Portugal, Berta, May, Patrick, Bobbili, Dheeraj Reddy, Radivojkov-Blagojevic, Milena, Lichtner, Peter, Singleton, Andrew B., Hernandez, Dena G., Edsall, Connor, Mellick, George D., Zimprich, Alexander, Pirker, Walter, Rogaeva, Ekaterina, Lang, Anthony E., Koks, Sulev, Taba, Pille, Lesage, Suzanne, Brice, Alexis, Corvol, Jean-Christophe, Chartier-Harlin, Marie-Christine, Mutez, Eugénie, Brockmann, Kathrin, Deutschländer, Angela B., Hadjigeorgiou, Georges M., Dardiotis, Efthimos, Stefanis, Leonidas, Simitsi, Athina Maria, Valente, Enza Maria, Petrucci, Simona, Duga, Stefano, Straniero, Letizia, Zecchinelli, Anna, Pezzoli, Gianni, Brighina, Laura, Ferrarese, Carlo, Annesi, Grazia, Quattrone, Andrea, Gagliardi, Monica, Matsuo, Hirotaka, Kawamura, Yusuke, Hattori, Nobutaka, Nishioka, Kenya, Chung, Sun Ju, Kim, Yun Joong, Kolber, Pierre, van de Warrenburg, Bart P. C., Bloem, Bastiaan R., Aasly, Jan, Toft, Mathias, Pihlstrøm, Lasse, Correia Guedes, Leonor, Ferreira, Joaquim J., Bardien, Soraya, Carr, Jonathan, Tolosa, Eduardo, Ezquerra, Mario, Pastor, Pau, Diez-Fairen, Monica, Wirdefeldt, Karin, Pedersen, Nancy L., Ran, Caroline, Belin, Andrea C., Puschmann, Andreas, Hellberg, Clara, Clarke, Carl E., Morrison, Karen E., Tan, Manuela, Krainc, Dimitri, Burbulla, Lena F., Farrer, Matt J., Krüger, Rejko, Gasser, Thomas, Sharma, Manu, Elbaz, Alexis, Genetics, The Comprehensive Unbiased Risk Factor Assessment For, and Consortium, Environment In Parkinson S Disease Courage-P. D.

Abstract

Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two-sample Mendelian randomization (MR). Methods We genotyped a well-established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage-PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95 confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P-difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society

Published
2022

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