Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

doi:10.1038/s41588-023-01584-8

Meta-Analysis

. 2024 Jan;56(1):27-36.

doi: 10.1038/s41588-023-01584-8. Epub 2023 Dec 28.

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Jonggeol Jeffrey Kim^#^{1

2}, Dan Vitale^#^{3

4

5}, Diego Véliz Otani^#^{6

7}, Michelle Mulan Lian^#^{8

9}, Karl Heilbron¹⁰; 23andMe Research Team; Hirotaka Iwaki^{3

4

5}, Julie Lake³, Caroline Warly Solsberg^{11

12

13}, Hampton Leonard^{3

4

5}, Mary B Makarious^{3

14

15}, Eng-King Tan¹⁶, Andrew B Singleton^{3

5}, Sara Bandres-Ciga^{3

5}, Alastair J Noyce¹⁷; Global Parkinson’s Genetics Program (GP2); Cornelis Blauwendraat^{18

19}, Mike A Nalls^{20

21

22}, Jia Nee Foo^{23

24}, Ignacio Mata²⁵

Collaborators, Affiliations

Collaborators

Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Paul Cannon, Daniella Coker, Gabriel Cuellar Partida, Devika Dhamija, Sayantan Das, Sarah L Elson, Nicholas Eriksson, Teresa Filshtein, Alison Fitch, Kipper Fletez-Brant, Pierre Fontanillas, Will Freyman, Julie M Granka, Alejandro Hernandez, Barry Hicks, David A Hinds, Ethan M Jewett, Yunxuan Jiang, Katelyn Kukar, Alan Kwong, Keng-Han Lin, Bianca A Llamas, Maya Lowe, Jey C McCreight, Matthew H McIntyre, Steven J Micheletti, Meghan E Moreno, Priyanka Nandakumar, Dominique T Nguyen, Elizabeth S Noblin, Jared O'Connell, Aaron A Petrakovitz, G David Poznik, Alexandra Reynoso, Madeleine Schloetter, Morgan Schumacher, Anjali J Shastri, Janie F Shelton, Jingchunzi Shi, Suyash Shringarpure, Qiaojuan Jane Su, Susana A Tat, Christophe Toukam Tchakouté, Vinh Tran, Joyce Y Tung, Xin Wang, Wei Wang, Catherine H Weldon, Peter Wilton, Corinna D Wong, Emilia M Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E Shepherd, Julie Hunter, Kishore Kumar, Melina Ellis, Miguel E Rentería, Sulev Koks, Alexander Zimprich, Artur F Schumacher-Schuh, Carlos Rieder, Paula Saffie Awad, Vitor Tumas, Sarah Camargos, Edward A Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, Maria Leonor Bustamante, Patricio Olguin, Pedro Chana, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzalo Arboleda, Jorge Orozc, Marlene Jimenez Del Rio, Alvaro Hernandez, Mohamed Salama, Walaa A Kamel, Yared Z Zewde, Alexis Brice, Jean-Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva-Juliane Vollstedt, Franziska Hopfner, Günter Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih-Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, Maria Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, K P Divya, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad-Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen-Yang Lim, Wael Mohamed, Yi Wen Tay, Daniel Martinez-Ramirez, Mayela Rodriguez-Violante, Paula Reyes-Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim J Anderson, Toni L Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola Ojo, Jan O Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Diego Veliz-Otani, Mario Cornejo-Olivas, Maria Leila Doquenia, Raymond Rosales, Angel Vinuela, Elena Iakovenko, Bashayer Al Mubarak, Muhammad Umair, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Alvarez, Janet Hoenicka, Katrin Beyer, Maria Teresa Periñan, Pau Pastor, Sarah El-Sadig, Kajsa Brolin, Christiane Zweier, Gerd Tinkhauser, Paul Krack, Chin-Hsien Lin, Hsiu-Chuan Wu, Pin-Jui Kung, Ruey-Meei Wu, Yihru Wu, Rim Amouri, Samia Ben Sassi, A Nazl Başak, Gencer Genc, Özgür Öztop Çakmak, Sibel Ertan, Alejandro Martínez-Carrasco, Anette Schrag, Anthony Schapira, Camille Carroll, Claire Bale, Donald Grosset, Eleanor J Stafford, Henry Houlden, Huw R Morris, John Hardy, Kin Ying Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick Alfryn Lewis, Rauan Kaiyrzhanov, Rimona Weil, Seth Love, Simon Stott, Simona Jasaityte, Sumit Dey, Vida Obese, Alberto Espay, Alyssa O'Grady, Andrew K Sobering, Bernadette Siddiqi, Bradford Casey, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Caroline B Pantazis, Charisse Comart, Claire Wegel, Deborah Hall, Dena Hernandez, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E Serrano, Honglei Chen, Ignacio F Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Joseph Jankovic, Joshua Shulman, Justin C Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin S Levine, Lana M Chahine, Laura Ibanez, Laurel Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew Koretsky, Megan J Puckelwartz, Miguel Inca-Martinez, Naomi Louie, Niccolò Emanuele Mencacci, Roger Albin, Roy Alcalay, Ruth Walker, Sohini Chowdhury, Sonya Dumanis, Steven Lubbe, Tao Xie, Tatiana Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Affiliations

¹ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. kimjoj@nih.gov.
² Preventive Neurology Unit, Centre for Prevention Diagnosis and Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, UK. kimjoj@nih.gov.
³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ Data Tecnica International, Washington, DC, USA.
⁵ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁶ Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
⁷ Institute for Genome Sciences, University of Maryland, Baltimore, MD, USA.
⁸ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
⁹ Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore.
¹⁰ 23andMe, Inc., Sunnyvale, CA, USA.
¹¹ Pharmaceutical Sciences and Pharmacogenomics, UCSF, San Francisco, CA, USA.
¹² Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
¹³ Memory and Aging Center, UCSF, San Francisco, CA, USA.
¹⁴ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
¹⁵ UCL Movement Disorders Centre, University College London, London, UK.
¹⁶ Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore.
¹⁷ Preventive Neurology Unit, Centre for Prevention Diagnosis and Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
¹⁸ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. cornelis.blauwendraat@nih.gov.
¹⁹ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. cornelis.blauwendraat@nih.gov.
²⁰ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. mike@datatecnica.com.
²¹ Data Tecnica International, Washington, DC, USA. mike@datatecnica.com.
²² Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. mike@datatecnica.com.
²³ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore. jianee.foo@ntu.edu.sg.
²⁴ Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore. jianee.foo@ntu.edu.sg.
²⁵ Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. matai@ccf.org.

^# Contributed equally.

PMID: 38155330
PMCID: PMC10786718
DOI: 10.1038/s41588-023-01584-8

Meta-Analysis

Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

Jonggeol Jeffrey Kim et al. Nat Genet. 2024 Jan.

. 2024 Jan;56(1):27-36.

doi: 10.1038/s41588-023-01584-8. Epub 2023 Dec 28.

Authors

Collaborators

Stella Aslibekyan, Adam Auton, Elizabeth Babalola, Robert K Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Paul Cannon, Daniella Coker, Gabriel Cuellar Partida, Devika Dhamija, Sayantan Das, Sarah L Elson, Nicholas Eriksson, Teresa Filshtein, Alison Fitch, Kipper Fletez-Brant, Pierre Fontanillas, Will Freyman, Julie M Granka, Alejandro Hernandez, Barry Hicks, David A Hinds, Ethan M Jewett, Yunxuan Jiang, Katelyn Kukar, Alan Kwong, Keng-Han Lin, Bianca A Llamas, Maya Lowe, Jey C McCreight, Matthew H McIntyre, Steven J Micheletti, Meghan E Moreno, Priyanka Nandakumar, Dominique T Nguyen, Elizabeth S Noblin, Jared O'Connell, Aaron A Petrakovitz, G David Poznik, Alexandra Reynoso, Madeleine Schloetter, Morgan Schumacher, Anjali J Shastri, Janie F Shelton, Jingchunzi Shi, Suyash Shringarpure, Qiaojuan Jane Su, Susana A Tat, Christophe Toukam Tchakouté, Vinh Tran, Joyce Y Tung, Xin Wang, Wei Wang, Catherine H Weldon, Peter Wilton, Corinna D Wong, Emilia M Gatto, Marcelo Kauffman, Samson Khachatryan, Zaruhi Tavadyan, Claire E Shepherd, Julie Hunter, Kishore Kumar, Melina Ellis, Miguel E Rentería, Sulev Koks, Alexander Zimprich, Artur F Schumacher-Schuh, Carlos Rieder, Paula Saffie Awad, Vitor Tumas, Sarah Camargos, Edward A Fon, Oury Monchi, Ted Fon, Benjamin Pizarro Galleguillos, Marcelo Miranda, Maria Leonor Bustamante, Patricio Olguin, Pedro Chana, Beisha Tang, Huifang Shang, Jifeng Guo, Piu Chan, Wei Luo, Gonzalo Arboleda, Jorge Orozc, Marlene Jimenez Del Rio, Alvaro Hernandez, Mohamed Salama, Walaa A Kamel, Yared Z Zewde, Alexis Brice, Jean-Christophe Corvol, Ana Westenberger, Anastasia Illarionova, Brit Mollenhauer, Christine Klein, Eva-Juliane Vollstedt, Franziska Hopfner, Günter Höglinger, Harutyun Madoev, Joanne Trinh, Johanna Junker, Katja Lohmann, Lara M Lange, Manu Sharma, Sergiu Groppa, Thomas Gasser, Zih-Hua Fang, Albert Akpalu, Georgia Xiromerisiou, Georgios Hadjigorgiou, Ioannis Dagklis, Ioannis Tarnanas, Leonidas Stefanis, Maria Stamelou, Efthymios Dadiotis, Alex Medina, Germaine Hiu-Fai Chan, Nancy Ip, Nelson Yuk-Fai Cheung, Phillip Chan, Xiaopu Zhou, Asha Kishore, K P Divya, Pramod Pal, Prashanth Lingappa Kukkle, Roopa Rajan, Rupam Borgohain, Mehri Salari, Andrea Quattrone, Enza Maria Valente, Lucilla Parnetti, Micol Avenali, Tommaso Schirinzi, Manabu Funayama, Nobutaka Hattori, Tomotaka Shiraishi, Altynay Karimova, Gulnaz Kaishibayeva, Cholpon Shambetova, Rejko Krüger, Ai Huey Tan, Azlina Ahmad-Annuar, Mohamed Ibrahim Norlinah, Nor Azian Abdul Murad, Shahrul Azmin, Shen-Yang Lim, Wael Mohamed, Yi Wen Tay, Daniel Martinez-Ramirez, Mayela Rodriguez-Violante, Paula Reyes-Pérez, Bayasgalan Tserensodnom, Rajeev Ojha, Tim J Anderson, Toni L Pitcher, Arinola Sanyaolu, Njideka Okubadejo, Oluwadamilola Ojo, Jan O Aasly, Lasse Pihlstrøm, Manuela Tan, Shoaib Ur-Rehman, Diego Veliz-Otani, Mario Cornejo-Olivas, Maria Leila Doquenia, Raymond Rosales, Angel Vinuela, Elena Iakovenko, Bashayer Al Mubarak, Muhammad Umair, Ferzana Amod, Jonathan Carr, Soraya Bardien, Beomseok Jeon, Yun Joong Kim, Esther Cubo, Ignacio Alvarez, Janet Hoenicka, Katrin Beyer, Maria Teresa Periñan, Pau Pastor, Sarah El-Sadig, Kajsa Brolin, Christiane Zweier, Gerd Tinkhauser, Paul Krack, Chin-Hsien Lin, Hsiu-Chuan Wu, Pin-Jui Kung, Ruey-Meei Wu, Yihru Wu, Rim Amouri, Samia Ben Sassi, A Nazl Başak, Gencer Genc, Özgür Öztop Çakmak, Sibel Ertan, Alejandro Martínez-Carrasco, Anette Schrag, Anthony Schapira, Camille Carroll, Claire Bale, Donald Grosset, Eleanor J Stafford, Henry Houlden, Huw R Morris, John Hardy, Kin Ying Mok, Mie Rizig, Nicholas Wood, Nigel Williams, Olaitan Okunoye, Patrick Alfryn Lewis, Rauan Kaiyrzhanov, Rimona Weil, Seth Love, Simon Stott, Simona Jasaityte, Sumit Dey, Vida Obese, Alberto Espay, Alyssa O'Grady, Andrew K Sobering, Bernadette Siddiqi, Bradford Casey, Brian Fiske, Cabell Jonas, Carlos Cruchaga, Caroline B Pantazis, Charisse Comart, Claire Wegel, Deborah Hall, Dena Hernandez, Ejaz Shiamim, Ekemini Riley, Faraz Faghri, Geidy E Serrano, Honglei Chen, Ignacio F Mata, Ignacio Juan Keller Sarmiento, Jared Williamson, Joseph Jankovic, Joshua Shulman, Justin C Solle, Kaileigh Murphy, Karen Nuytemans, Karl Kieburtz, Katerina Markopoulou, Kenneth Marek, Kristin S Levine, Lana M Chahine, Laura Ibanez, Laurel Screven, Lauren Ruffrage, Lisa Shulman, Luca Marsili, Maggie Kuhl, Marissa Dean, Mathew Koretsky, Megan J Puckelwartz, Miguel Inca-Martinez, Naomi Louie, Niccolò Emanuele Mencacci, Roger Albin, Roy Alcalay, Ruth Walker, Sohini Chowdhury, Sonya Dumanis, Steven Lubbe, Tao Xie, Tatiana Foroud, Thomas Beach, Todd Sherer, Yeajin Song, Duan Nguyen, Toan Nguyen, Masharip Atadzhanov

Affiliations

¹ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. kimjoj@nih.gov.
² Preventive Neurology Unit, Centre for Prevention Diagnosis and Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, UK. kimjoj@nih.gov.
³ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
⁴ Data Tecnica International, Washington, DC, USA.
⁵ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
⁶ Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
⁷ Institute for Genome Sciences, University of Maryland, Baltimore, MD, USA.
⁸ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
⁹ Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore.
¹⁰ 23andMe, Inc., Sunnyvale, CA, USA.
¹¹ Pharmaceutical Sciences and Pharmacogenomics, UCSF, San Francisco, CA, USA.
¹² Department of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
¹³ Memory and Aging Center, UCSF, San Francisco, CA, USA.
¹⁴ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
¹⁵ UCL Movement Disorders Centre, University College London, London, UK.
¹⁶ Department of Neurology, National Neuroscience Institute, Duke NUS Medical School, Singapore, Singapore.
¹⁷ Preventive Neurology Unit, Centre for Prevention Diagnosis and Detection, Wolfson Institute of Population Health, Queen Mary University of London, London, UK.
¹⁸ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. cornelis.blauwendraat@nih.gov.
¹⁹ Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. cornelis.blauwendraat@nih.gov.
²⁰ Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. mike@datatecnica.com.
²¹ Data Tecnica International, Washington, DC, USA. mike@datatecnica.com.
²² Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. mike@datatecnica.com.
²³ Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore. jianee.foo@ntu.edu.sg.
²⁴ Genome Institute of Singapore, Agency for Science, Technology and Research, A*STAR, Singapore, Singapore. jianee.foo@ntu.edu.sg.
²⁵ Genomic Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA. matai@ccf.org.

^# Contributed equally.

PMID: 38155330
PMCID: PMC10786718
DOI: 10.1038/s41588-023-01584-8

Abstract

Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations.

PubMed Disclaimer

Conflict of interest statement

K.H. and members of the 23andMe Research Team are employed by and hold stock or stock options in 23andMe. M.A.N.’s participation in this project was part of a competitive contract awarded to Data Tecnica International by the NIH to support open science research; he also currently serves on the scientific advisory board for Clover Therapeutics and is an advisor to Neuron23. A.J.N. reports consultancy and personal fees from AstraZeneca, AbbVie, Profile, Roche, Biogen, UCB, Bial, Charco Neurotech, uMedeor, Alchemab and Britannia outside the submitted work. The other authors declare no competing interests.

Figures

**Fig. 1. MAMA study design.**
Top panel: four ancestry groups used in the meta-analysis. Middle panel: MAMA and the two methods used. Random-effect (top) is better suited for risk variants with homogeneous effect direction across different ancestries, whereas MR-MEGA (bottom) can identify risk variants with heterogeneous effects due to population stratification introduced by ancestry differences. The densely dashed lines indicate Bonferroni adjusted suggestive threshold of two-sided P < 1 × 10⁻⁶, and the loosely dashed lines indicate Bonferroni adjusted significant threshold of two-sided P < 5 × 10⁻⁹. Bottom panel: downstream analyses and their examples. Created with Biorender.com.

**Fig. 2. Manhattan plots of the meta-analysis results across 2,525,730 participants.**
a, Random-effects model test. b, MR-MEGA meta-regression test (chi-squared test with df = 4). The x axis shows chromosome and base pair positions of each variant tested in the meta-analyses. The y axis shows the two-sided P value with no multiple-test correction in the −log₁₀ scale. Orange horizontal dashed line indicates the Bonferroni-adjusted significant threshold of P < 5 × 10⁻⁹. Gray horizontal dashed line indicates the truncation line, where all −log₁₀ P values greater than 40 were truncated to 40 for visual clarity. Novel loci are highlighted in red and annotated with the nearest protein coding gene.

**Fig. 3. Heterogeneity upset plots.**
a, Top variants per novel loci. b, Top variants per MR-MEGA identified locus with moderate to high heterogeneity (I² > 30). The top bar plot illustrates heterogeneity with dark blue indicating ancestry heterogeneity proportion and light blue indicating other residual heterogeneity proportion. The bottom plot shows the subcohort level beta values with blue indicating positive and red indicating negative effect directions. Three variants with greater than 30% I² total heterogeneity were only identified in the MR-MEGA meta-analysis method, whereas little to no heterogeneity is observed in loci identified in random effect.

See this image and copyright information in PMC

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References

1. Nalls MA, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091–1102. doi: 10.1016/S1474-4422(19)30320-5. - DOI - PMC - PubMed
1. Foo JN, et al. Identification of risk loci for Parkinson disease in Asians and comparison of risk between Asians and Europeans: a genome-wide association study. JAMA Neurol. 2020;77:746–754. doi: 10.1001/jamaneurol.2020.0428. - DOI - PMC - PubMed
1. Loesch DP, et al. Characterizing the genetic architecture of Parkinson’s disease in Latinos. Ann. Neurol. 2021;90:353–365. doi: 10.1002/ana.26153. - DOI - PMC - PubMed
1. Rajan R, et al. Genetic architecture of Parkinson’s disease in the Indian population: harnessing genetic diversity to address critical gaps in Parkinson’s disease research. Front. Neurol. 2020;11:524. doi: 10.3389/fneur.2020.00524. - DOI - PMC - PubMed
1. Global Parkinson’s Genetics Program. GP2: The Global Parkinson’s Genetics Program. Mov. Disord. 36, 842–851 (2021). - PMC - PubMed

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[1] Nalls MA, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091–1102. doi: 10.1016/S1474-4422(19)30320-5. - DOI - PMC - PubMed

[2] Nalls MA, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091–1102. doi: 10.1016/S1474-4422(19)30320-5. - DOI - PMC - PubMed

[3] Foo JN, et al. Identification of risk loci for Parkinson disease in Asians and comparison of risk between Asians and Europeans: a genome-wide association study. JAMA Neurol. 2020;77:746–754. doi: 10.1001/jamaneurol.2020.0428. - DOI - PMC - PubMed

[4] Foo JN, et al. Identification of risk loci for Parkinson disease in Asians and comparison of risk between Asians and Europeans: a genome-wide association study. JAMA Neurol. 2020;77:746–754. doi: 10.1001/jamaneurol.2020.0428. - DOI - PMC - PubMed

[5] Loesch DP, et al. Characterizing the genetic architecture of Parkinson’s disease in Latinos. Ann. Neurol. 2021;90:353–365. doi: 10.1002/ana.26153. - DOI - PMC - PubMed

[6] Loesch DP, et al. Characterizing the genetic architecture of Parkinson’s disease in Latinos. Ann. Neurol. 2021;90:353–365. doi: 10.1002/ana.26153. - DOI - PMC - PubMed

[7] Rajan R, et al. Genetic architecture of Parkinson’s disease in the Indian population: harnessing genetic diversity to address critical gaps in Parkinson’s disease research. Front. Neurol. 2020;11:524. doi: 10.3389/fneur.2020.00524. - DOI - PMC - PubMed

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Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

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Multi-ancestry genome-wide association meta-analysis of Parkinson's disease

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