285811 20260401142103.0 10.1038/s41531-026-01265-3 doi DZNE-2026-00347 610 Lim, Kai Shi 0 Association of LRRK2 p.A419V with Parkinson’s Disease in East Asians and analysis of age at onset [London] 2026 Springer Nature article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1775045897_18971 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Common and rare variants in LRRK2 influence Parkinson’s disease (PD) risk across diverse populations, and in this study, the rare p.A419V variant was investigated across multiple ancestry cohorts comprising over 200,000 PD cases and controls. In cases of East Asian (EAS) ancestry, p.A419V was significantly associated with increased risk of PD (OR = 2.9; 95% CI: 1.66–5.10; p = 0.0002), and was not in linkage disequilibrium with other LRRK2 coding variants. The variant was significantly associated with a lower age at PD onset in the study cohort, while a meta-analysis of the EAS cases indicated a similar, albeit non-significant trend. LRRK2 protein modelling prediction indicated that binding sites for RAB8A, RAB29 and RAB32 were in close proximity to the p.A419V variant within the ARM domain. Together, these findings confirm the p.A419V as a significant PD risk factor in EAS populations, as well as highlight disease-relevant variants in the ARM domain and the link with LRRK2-RAB signaling. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 899 - ohne Topic (POF4-899) G:(DE-HGF)POF4-899 POF4-899 POF IV 1 Dataset connected to CrossRef, Journals: pub.dzne.de Periñan, Maria Teresa 1 Chew, Elaine Guo Yan 2 Lee, Paul Suhwan 3 Akçimen, Fulya 4 Lim, Jia Lun 5 Koretsky, Mathew J. 6 Funayama, Manabu 7 Yoshino, Hiroyo 8 Hattori, Nobutaka 9 Kaiyrzhanov, Rauan 10 Houlden, Henry 11 Isayan, Mariam 12 Tay, Yi Wen 13 Toh, Tzi Shin 14 Lit, Lei-Cheng 15 Khairul Anuar, Anis Nadhirah 16 Ding, Hans Xing 17 Screven, Laurel 18 Ibrahim, Norlinah Mohamed 19 Lin, Chin-Hsien 20 Kim, Han-Joon 21 Lee, Jee-Young 22 Chung, Sun Ju 23 Foo, Jia Nee 24 Tan, Eng-King 25 Lim, Shen-Yang 26 Tan, Ai Huey 27 Bandres-Ciga, Sara 28 Ahmad-Annuar, Azlina 29 Yan Chew, Elaine Guo 30 Khairul Anuar, Anis Nadhirah 31 Rizig, Mie 32 Okubadejo, Njideka 33 Gatto, Emilia M. 34 Kauffman, Marcelo 35 Khachatryan, Samson 36 Tavadyan, Zaruhi 37 Shepherd, Claire E. 38 Hunter, Julie 39 Kumar, Kishore 40 Ellis, Melina 41 Rentería, Miguel E. 42 Koks, Sulev 43 Zimprich, Alexander 44 Rieder, Carlos 45 Tumas, Vitor 46 Camargos, Sarah 47 Fon, Edward A. 48 Fon, Ted 49 Monchi, Oury 50 Galleguillos, Benjamin Pizarro 51 Olguin, Patricio 52 Miranda, Marcelo 53 Bustamante, Maria Leonor 54 Tang, Beisha 55 Shang, Huifang 56 Guo, Jifeng 57 Chan, Piu 58 Luo, Wei 59 Arboleda, Gonzalo 60 Orozco, Jorge 61 del Rio, Marlene Jimenez 62 Hernandez, Alvaro 63 Salama, Mohamed 64 Kamel, Walaa A. 65 Zewde, Yared Z. 66 Brice, Alexis 67 Corvol, Jean-Christophe 68 Westenberger, Ana 69 Klein, Christine 70 Vollstedt, Eva-Juliane 71 Madoev, Harutyun 72 Trinh, Joanne 73 Junker, Johanna 74 Lohmann, Katja 75 Illarionova, Anastasia P:(DE-2719)2812762 76 dzne Mollenhauer, Brit P:(DE-2719)9001340 77 dzne Hopfner, Franziska P:(DE-2719)9003372 78 dzne Höglinger, Günter P:(DE-2719)2811373 79 dzne Lange, Lara M. 80 Sharma, Manu 81 Gasser, Thomas P:(DE-2719)2320009 82 dzne Fang, Zih-Hua P:(DE-2719)9001362 83 dzne Groppa, Sergio 84 Akpalu, Albert 85 Xiromerisiou, Georgia 86 Hadjigeorgiou, Georgios 87 Dardiotis, Efthymios 88 Dagklis, Ioannis 89 Tarnanas, Ioannis 90 Stefanis, Leonidas 91 Stamelou, Maria 92 Medina, Alex 93 Chan, Germaine Hiu-Fai 94 Cheung, Nelson Yuk-Fai 95 Ip, Nancy 96 Chan, Phillip 97 Zhou, Xiaopu 98 Kishore, Asha 99 Divya, K. P. 100 Pal, Pramod 101 Kukkle, Prashanth Lingappa 102 Rajan, Roopa 103 Borgohain, Rupam 104 Salari, Mehri 105 Quattrone, Andrea P:(DE-2719)9002627 106 dzne Valente, Enza Maria 107 Avenali, Micol 108 Parnetti, Lucilla 109 Schirinzi, Tommaso 110 Shiraishi, Tomotaka 111 Karimova, Altynay 112 Kaishibayeva, Gulnaz 113 Shambetova, Cholpon 114 Krüger, Rejko 115 Abdul Murad, Nor Azian 116 Azmin, Shahrul 117 Mohamed, Wael 118 Martinez-Ramirez, Daniel 119 Rodriguez-Violante, Mayela 120 Reayes-Perez, Paula 121 Tserensodnom, Bayasgalan 122 Ojha, Rajeev 123 Anderson, Tim J. 124 Pitcher, Toni L. 125 Ojo, Oluwadamilola 126 Aasly, Jan O. 127 Pihlstrøm, Lasse 128 Tan, Manuela 129 Ur-Rehman, Shoaib 130 Cornejo-Olivas, Mario 131 Doquenia, Maria Leila 132 Rosales, Raymond 133 Vinuela, Angel 134 Iakovenko, Elena 135 Mubarak, Bashayer Al 136 Umair, Muhammad 137 Amod, Ferzana 138 Carr, Jonathan 139 Bardien, Soraya 140 Jeon, Beomseok 141 Kim, Yun Joong 142 Cubo, Esther 143 Alvarez, Ignacio 144 Hoenicka, Janet 145 Beyer, Katrin 146 Pastor, Pau 147 El-Sadig, Sarah 148 Zweier, Christiane 149 Krack, Paul 150 Wu, Ruey-Meei 151 Wu, Hsiu-Chuan 152 Wu, Yih-Ru 153 Kung, Pin-Jui 154 Wu, Serena 155 Amouri, Rim 156 Sassi, Samia Ben 157 Başak, A. Nazl 158 Çakmak, Özgür Öztop 159 Ertan, Sibel 160 Genc, Gencer 161 Martínez-Carrasco, Alejandro 162 Schrag, Anette 163 Schapira, Anthony 164 Stafford, Eleanor J. 165 Morris, Huw 166 Hardy, John 167 Wood, Nicholas 168 Okunoye, Olaitan 169 Weil, Rimona 170 Jasaitye, Simona 171 Obese, Vida 172 Carroll, Camille 173 Bale, Claire 174 Grosset, Donald 175 Mok, Kin Y. 176 Williams, Nigel 177 Lewis, Patrick A. 178 Love, Seth 179 Stott, Simon 180 Espay, Alberto 181 Marsili, Luca 182 O’Grady, Alyssa 183 Siddiqi, Bernadette 184 Casey, Bradford 185 Fiske, Brian 186 Comart, Charisse 187 Solle, Justin C. 188 Murphy, Kaileigh 189 Kuhl, Maggie 190 Louie, Naomi 191 Chowdhury, Sohini 192 Sherer, Todd 193 Sobering, Andrew K. 194 Jonas, Cabell 195 Cruchaga, Carlos 196 Pantazis, Caroline B. 197 Wegel, Claire 198 Hall, Deborah 199 Shamim, Ejaz 200 Williamson, Jared 201 Riley, Ekemini 202 Dumanis, Sonya 203 Serrano, Geidy E. 204 Beach, Thomas 205 Chen, Honglei 206 Keller Sarmiento, Ignacio Juan 207 Mencacci, Niccolò E. 208 Lubbe, Steven 209 Jankovic, Joseph 210 Inca-Martinez, Miguel 211 Shulman, Joshua 212 Nuytemans, Karen 213 Kieburtz, Karl 214 Markopoulou, Katerina 215 Marek, Kenneth 216 Chahine, Lana M. 217 Ruffrage, Lauren 218 Dean, Marissa 219 Shulman, Lisa 220 Albin, Roger 221 Alcalay, Roy 222 Walker, Ruth 223 Xie, Tao 224 Foroud, Tatiana 225 Nguyen, Duan 226 Nguyen, Toan 227 Atadzhanov, Masharip 228 10.1038/s41531-026-01265-3 Vol. 12, no. 1, p. 51 PERI:(DE-600)2819218-7 1 51 npj Parkinson's Disease 12 2026 2373-8057 http://pub.dzne.de/record/285811/files/DZNE-2026-00347.pdf Restricted http://pub.dzne.de/record/285811/files/DZNE-2026-00347.pdf?subformat=pdfa pdfa Restricted Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 76 P:(DE-2719)2812762 External Institute I:(DE-HGF)0 Extern 77 P:(DE-2719)9001340 External Institute I:(DE-HGF)0 Extern 78 P:(DE-2719)9003372 External Institute I:(DE-HGF)0 Extern 79 P:(DE-2719)2811373 External Institute I:(DE-HGF)0 Extern 82 P:(DE-2719)2320009 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 83 P:(DE-2719)9001362 External Institute I:(DE-HGF)0 Extern 106 P:(DE-2719)9002627 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 DE-HGF Programmungebundene Forschung ohne Programm G:(DE-HGF)POF4-890 G:(DE-HGF)POF4-899 G:(DE-HGF)POF4 G:(DE-HGF)POF4-800 G:(DE-HGF)POF ohne Topic 1 JCR StatID:(DE-HGF)0100 StatID NPJ PARKINSONS DIS : 2022 2024-12-11 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-11 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-11 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2024-04-10T15:43:48Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2024-04-10T15:43:48Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Anonymous peer review 2024-04-10T15:43:48Z Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2024-04-10T15:43:48Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-11 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-11 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-11 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-11 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-11 IF >= 5 StatID:(DE-HGF)9905 StatID NPJ PARKINSONS DIS : 2022 2024-12-11 Article Processing Charges StatID:(DE-HGF)0561 StatID 2024-12-11 Fees StatID:(DE-HGF)0700 StatID 2024-12-11 I:(DE-2719)1210000 AG Gasser Parkinson Genetics 0 I:(DE-2719)1240005 ICRU Core ICRU 1 journal EDITORS VDBINPRINT I:(DE-2719)1210000 I:(DE-2719)1240005 UNRESTRICTED