265764 20240112171355.0 10.1016/S1474-4422(23)00283-1 doi pmid:37633302 pmid pmc:PMC10593199 pmc 1474-4422 ISSN 1474-4465 ISSN altmetric:153257564 altmetric DZNE-2023-01035 English 610 Rizig, Mie 0 Identification of genetic risk loci and causal insights associated with Parkinson's disease in African and African admixed populations: a genome-wide association study. London 2023 Lancet Publ. Group article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1700061746_31971 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote An understanding of the genetic mechanisms underlying diseases in ancestrally diverse populations is an important step towards development of targeted treatments. Research in African and African admixed populations can enable mapping of complex traits, because of their genetic diversity, extensive population substructure, and distinct linkage disequilibrium patterns. We aimed to do a comprehensive genome-wide assessment in African and African admixed individuals to better understand the genetic architecture of Parkinson's disease in these underserved populations.We performed a genome-wide association study (GWAS) in people of African and African admixed ancestry with and without Parkinson's disease. Individuals were included from several cohorts that were available as a part of the Global Parkinson's Genetics Program, the International Parkinson's Disease Genomics Consortium Africa, and 23andMe. A diagnosis of Parkinson's disease was confirmed clinically by a movement disorder specialist for every individual in each cohort, except for 23andMe, in which it was self-reported based on clinical diagnosis. We characterised ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation, and enzymatic activity.We included 197 918 individuals (1488 cases and 196 430 controls) in our genome-wide analysis. We identified a novel common risk factor for Parkinson's disease (overall meta-analysis odds ratio for risk of Parkinson's disease 1·58 [95% CI 1·37-1·80], p=2·397 × 10-14) and age at onset at the GBA1 locus, rs3115534-G (age at onset β=-2·00 [SE=0·57], p=0·0005, for African ancestry; and β=-4·15 [0·58], p=0·015, for African admixed ancestry), which was rare in non-African or non-African admixed populations. Downstream short-read and long-read whole-genome sequencing analyses did not reveal any coding or structural variant underlying the GWAS signal. The identified signal seems to be associated with decreased glucocerebrosidase activity.Our study identified a novel genetic risk factor in GBA1 in people of African ancestry, which has not been seen in European populations, and it could be a major mechanistic basis of Parkinson's disease in African populations. This population-specific variant exerts substantial risk on Parkinson's disease as compared with common variation identified through GWAS and it was found to be present in 39% of the cases assessed in this study. This finding highlights the importance of understanding ancestry-specific genetic risk in complex diseases, a particularly crucial point as the Parkinson's disease field moves towards targeted treatments in clinical trials. The distinctive genetics of African populations highlights the need for equitable inclusion of ancestrally diverse groups in future trials, which will be a valuable step towards gaining insights into novel genetic determinants underlying the causes of Parkinson's disease. This finding opens new avenues towards RNA-based and other therapeutic strategies aimed at reducing lifetime risk of Parkinson's disease.The Global Parkinson's Genetics Program, which is funded by the Aligning Science Across Parkinson's initiative, and The Michael J Fox Foundation for Parkinson's Research. 354 - Disease Prevention and Healthy Aging (POF4-354) G:(DE-HGF)POF4-354 POF4-354 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Parkinson Disease: ethnology MeSH Humans MeSH Parkinson Disease: genetics MeSH Genome-Wide Association Study MeSH Genetic Loci MeSH Linkage Disequilibrium MeSH Black People: genetics MeSH Polymorphism, Single Nucleotide: genetics MeSH Genetic Predisposition to Disease: genetics MeSH African People: genetics MeSH GBA protein, human EC 3.2.1.45 NLM Chemicals Bandres-Ciga, Sara 1 Makarious, Mary B 2 Ojo, Oluwadamilola Omolara 3 Crea, Peter Wild 4 Abiodun, Oladunni Victoria 5 Levine, Kristin S 6 Abubakar, Sani Atta 7 Achoru, Charles Obiora 8 Vitale, Dan 9 Adeniji, Olaleye Akinmola 10 Agabi, Osigwe Paul 11 Koretsky, Mathew J 12 Agulanna, Uchechi 13 Hall, Deborah A 14 Akinyemi, Rufus Olusola 15 Xie, Tao 16 Ali, Mohammed Wulgo 17 Shamim, Ejaz A 18 Ani-Osheku, Ifeyinwa 19 Padmanaban, Mahesh 20 Arigbodi, Ohwotemu Michael 21 Standaert, David G 22 Bello, Abiodun Hamzat 23 Dean, Marissa N 24 Erameh, Cyril Oshomah 25 Elsayed, Inas 26 Farombi, Temitope Hannah 27 Okunoye, Olaitan 28 Fawale, Michael Bimbola 29 Billingsley, Kimberley J 30 Imarhiagbe, Frank Aiwansoba 31 Jerez, Pilar Alvarez 32 Iwuozo, Emmanuel Uzodinma 33 Baker, Breeana 34 Komolafe, Morenikeji Adeyoyin 35 Malik, Laksh 36 Nwani, Paul Osemeke 37 Daida, Kensuke 38 Nwazor, Ernest Okwundu 39 Miano-Burkhardt, Abigail 40 Nyandaiti, Yakub Wilberforce 41 Fang, Zih-Hua P:(DE-2719)9001362 42 dzne Obiabo, Yahaya Olugbo 43 Kluss, Jillian H 44 Odeniyi, Olanike Adedoyin 45 Hernandez, Dena G 46 Odiase, Francis Ehidiamen 47 Tayebi, Nahid 48 Ojini, Francis Ibe 49 Sidranksy, Ellen 50 Onwuegbuzie, Gerald Awele 51 D'Souza, Andrea M 52 Osaigbovo, Godwin Osawaru 53 Berhe, Bahafta 54 Osemwegie, Nosakhare 55 Reed, Xylena 56 Oshinaike, Olajumoke Olufemi 57 Leonard, Hampton L 58 Otubogun, Folajimi Morenikeji 59 Alvarado, Chelsea X 60 Oyakhire, Shyngle Imiewan 61 Ozomma, Simon Izuchukwu 62 Samuel, Sarah Chabiri 63 Taiwo, Funmilola Tolulope 64 Wahab, Kolawole Wasiu 65 Zubair, Yusuf Agboola 66 Iwaki, Hirotaka 67 Kim, Jonggeol Jeffrey 68 Morris, Huw R 69 Hardy, John 70 Nalls, Mike A 71 Heilbron, Karl 72 Norcliffe-Kaufmann, Lucy 73 Network, Nigeria Parkinson Disease Research 74 Collaboration Author Africa, International Parkinson's Disease Genomics Consortium 75 Collaboration Author Black 76 Group, African American Connections to Parkinson's Disease Study 77 Collaboration Author Team, 23andMe Research 78 Collaboration Author Blauwendraat, Cornelis 79 Houlden, Henry 80 Singleton, Andrew 81 Okubadejo, Njideka Ulunma 82 Program, Global Parkinson's Genetics 83 Collaboration Author Okubadejo, Njideka 84 Contributor Ojo, Oluwadamilola 85 Contributor Abiodun, Oladunni 86 Contributor Achoru, Charles 87 Contributor Agabi, Osigwe 88 Contributor Agulanna, Uchechi 89 Contributor Akinyemi, Rufus 90 Contributor Ali, Mohammed 91 Contributor Ani-Osheku, Ifeyinwa 92 Contributor Arigbodi, Ohwotemu 93 Contributor Bello, Abiodun 94 Contributor Erameh, Cyril 95 Contributor Farombi, Temitope 96 Contributor Fawale, Michael 97 Contributor Imarhiagbe, Frank 98 Contributor Iwuozo, Emmanuel 99 Contributor Komolafe, Morenikeji 100 Contributor Nwani, Paul 101 Contributor Nwazor, Ernest 102 Contributor Nyandaiti, Yakub 103 Contributor Obiabo, Yahaya 104 Contributor Odeniyi, Olanike 105 Contributor Odiase, Francis 106 Contributor Ojini, Francis 107 Contributor Onwuegbuzie, Gerald 108 Contributor Osaigbovo, Godwin 109 Contributor Osemwegie, Nosakhare 110 Contributor Oshinaike, Olajumoke 111 Contributor Otubogun, Folajimi 112 Contributor Oyakhire, Shyngle 113 Contributor Ozomma, Simon 114 Contributor Samuel, Sarah 115 Contributor Taiwo, Funmilola 116 Contributor Wahab, Kolawole 117 Contributor Zubair, Yusuf 118 Contributor Gams Massi, Daniel 119 Contributor Gueumekane Bila Lamou, Eric 120 Contributor Njamnshi Nfor, Leonard 121 Contributor Magnerou, Mélanie Annick 122 Contributor Fogang Fogoum, Yannick 123 Contributor Shalash, Ali 124 Contributor El-FawaI, Hassan 125 Contributor Khedr, Eman 126 Contributor Fawi, Gharib 127 Contributor A Eltantawi, Mohamed 128 Contributor Salama, Mohamed 129 Contributor El-Jaafary, Shaimaa 130 Contributor Hamed, Sharifa 131 Contributor Tafesse Mengesha, Abenet 132 Contributor Alemayehu Ayele, Biniyam 133 Contributor Melka Oda, Dereje 134 Contributor Zenebe Zewde, Yared 135 Contributor Debebe Gelan, Yohanesse 136 Contributor AkpaIu, Albert 137 Contributor Charway-Felli, Augustina 138 Contributor Stephen Sarfo, Fred 139 Contributor Adjei, Patrick 140 Contributor Obese, Vida 141 Contributor Bocoum, Abdoulaye 142 Contributor Koita, Abdou 143 Contributor Oumar Guinto, Cheick 144 Contributor Coulibaly, Toumany 145 Contributor Maiga, Youssoufa 146 Contributor Kone, Zaynab 147 Contributor Bell, Abiodun 148 Contributor Agabi, Osigwe 149 Contributor Adebowale, Akintunde A 150 Contributor Akpekpe, John 151 Contributor Lyagba, Alagoma 152 Contributor Wulgo, Ali Mohammed 153 Contributor Ani-Osheku, Ifeyinwa 154 Contributor Arabambi, Babawale 155 Contributor Achoru, Charles 156 Contributor Agu, Christian 157 Contributor Erameh, Cyril 158 Contributor Iwuozo, Emmanuel 159 Contributor Nwazor, Ernest 160 Contributor Fawale, Michael 161 Contributor Otubogun, Folajimi 162 Contributor Odiase, Francis 163 Contributor Dike, Franklin 164 Contributor Ishola, Ismail 165 Contributor Wahab, Kolawole 166 Contributor Abiodun, Kehinde 167 Contributor Komolafe, Morenikeji 168 Contributor Okubadejo, Njideka 169 Contributor Obiabo, Yahaya 170 Contributor Arigbodi, Ohwotemu 171 Contributor Oshinaike, Olajumoke 172 Contributor Osemwegie, Nosakhare 173 Contributor Ekenze, Oluchi 174 Contributor Ojo, Oluwadamilola 175 Contributor Agabi Osigwe, Paul 176 Contributor Nwani, Paul 177 Contributor Balarabe, Salisu 178 Contributor Abubakar, Sani 179 Contributor Williams, Uduak 180 Contributor Abiodun, Oladunni 181 Contributor Zubair, Yusuf 182 Contributor Fall, Maouly 183 Contributor Mamadou Diop, Alassane 184 Contributor Hilaire Dominique, Ewodo Touna 185 Contributor Mochan, Andre 186 Contributor Modi, Girish 187 Contributor Dindayal, Saiesha 188 Contributor Ali Awadelkareem, Eman 189 Contributor Elsayed, Inas 190 Contributor Dahawi, Maha 191 Contributor Awadelkareem, Mosab Ali 192 Contributor Misbah, Sarah 193 Contributor Mushengez, Brighton 194 Contributor Kimambo, Henrika 195 Contributor Msango, Leonard 196 Contributor Adebayo, Philip 197 Contributor OKeng, Kigocha 198 Contributor Diekker, Marieke 199 Contributor URassa, Sarah 200 Contributor Gouider, Riadh 201 Contributor Ben Djebara, Mouna 202 Contributor Gargouri, Amina 203 Contributor Kacem, Imen 204 Contributor Nasri, Amina 205 Contributor Mrabet, Saloua 206 Contributor Sghaier, Ikram 207 Contributor Mkada, Imen 208 Contributor Atadzhanov, Masharip 209 Contributor Chishimba, Lorraine 210 Contributor Rizig, Mie 211 Contributor Jama, Fatumah 212 Contributor Okunoye, Olaitan 213 Contributor Hardy, John 214 Contributor Houlden, Henry 215 Contributor Singleton, Andrew 216 Contributor Nalls, Mike 217 Contributor Shamim, Ejaz 218 Contributor Jonas, Cabell 219 Contributor Williamson, Jared 220 Contributor Hall, Deborah A 221 Contributor Rosenbaum, Marc 222 Contributor Davis, Staci 223 Contributor Dean, Marissa 224 Contributor Cromer, Candace 225 Contributor Smith, Jenna 226 Contributor Ruffrage, Lauren 227 Contributor Richardson, Joseph 228 Contributor Sipma, Rebeka 229 Contributor Xie, Tao 230 Contributor Padmanaban, Manesh 231 Contributor Warren, Natalie 232 Contributor Mercado, Tomas 233 Contributor Disbrow, Elizabeth 234 Contributor Chauppeta, Brian 235 Contributor Thomas-Dean, Fermine 236 Contributor Toms, Jamie 237 Contributor Lofton, Katelyn 238 Contributor Rawls, Ashley 239 Contributor Rizer, Kyle 240 Contributor Black, Nieci 241 Contributor Solle, Justin 242 Contributor O'Grady, Alyssa 243 Contributor Sherer, Todd 244 Contributor Fiske, Brian 245 Contributor Başak, A Nazlı 246 Contributor Tan, Ai Huey 247 Contributor Noyce, Alastair 248 Contributor Akpalu, Albert 249 Contributor Espay, Alberto 250 Contributor Martínez-Carrasco, Alejandro 251 Contributor Medina, Alex 252 Contributor Zimprich, Alexander 253 Contributor Brice, Alexis 254 Contributor Karimova, Altynay 255 Contributor Hernandez, Alvaro 256 Contributor O'Grady, Alyssa 257 Contributor Illarionova, Anastasia 258 Contributor Quattrone, Andrea 259 Contributor Singleton, Andrew B 260 Contributor Sobering, Andrew K 261 Contributor Vinuela, Angel 262 Contributor Sanyaolu, Arinola 263 Contributor Schumacher-Schuh, Artur F 264 Contributor Kishore, Asha 265 Contributor Ahmad-Annuar, Azlina 266 Contributor Al Mubarak, Bashayer 267 Contributor Tang, Beisha 268 Contributor Pizarro Galleguillos, Benjamin 269 Contributor Jeon, Beomseok 270 Contributor Siddiqi, Bernadette 271 Contributor Casey, Bradford 272 Contributor Fiske, Brian 273 Contributor Mollenhauer, Brit 274 Contributor Jonas, Cabell 275 Contributor Carroll, Camille 276 Contributor Rieder, Carlos 277 Contributor Pantazis, Caroline B 278 Contributor Comart, Charisse 279 Contributor Lin, Chin-Hsien 280 Contributor Klein, Christine 281 Contributor Bale, Claire 282 Contributor Shepherd, Claire E 283 Contributor Wegel, Claire 284 Contributor Blauwendraat, Cornelis 285 Contributor Vitale, Dan 286 Contributor Martinez-Ramirez, Daniel 287 Contributor Hall, Deborah 288 Contributor Hernandez, Dena 289 Contributor Kp, Divya 290 Contributor Nguyen, Duan 291 Contributor Fon, Edward A 292 Contributor Dadiotis, Efthymios 293 Contributor Shamim, Ejaz 294 Contributor Riley, Ekemini 295 Contributor Iakovenko, Elena 296 Contributor Stafford, Ellie 297 Contributor Gatto, Emilia M 298 Contributor Valente, Enza Maria 299 Contributor Vollstedt, Eva-Juliane 300 Contributor Faghri, Faraz 301 Contributor Genc, Gencer 302 Contributor Xiromerisiou, Georgia 303 Contributor Hadjigorgiou, Georgios 304 Contributor Hiu-Fai Chan, Germaine 305 Contributor Arboleda, Gonzalo 306 Contributor Kaishibayeva, Gulnaz 307 Contributor Höglinger, Günter 308 Contributor Leonard, Hampton 309 Contributor Madoev, Harutyun 310 Contributor Houlden, Henry 311 Contributor Iwaki, Hirotaka 312 Contributor Chen, Honglei 313 Contributor Wu, Hsiu-Chuan 314 Contributor Shang, Huifang 315 Contributor Morris, Huw R 316 Contributor F Mata, Ignacio 317 Contributor Keller Sarmiento, Ignacio Juan 318 Contributor Dagklis, Ioannis 319 Contributor Tarnanas, Ioannis 320 Contributor Aasly, Jan O 321 Contributor Hoenicka, Janet 322 Contributor Williamson, Jared 323 Contributor Corvol, Jean-Christophe 324 Contributor Foo, Jia Nee 325 Contributor Guo, Jifeng 326 Contributor Junker, Johanna 327 Contributor Hardy, John 328 Contributor Carr, Jonathan 329 Contributor Kim, Jonggeol Jeff 330 Contributor Orozco, Jorge 331 Contributor Jankovic, Joseph 332 Contributor Shulman, Joshua 333 Contributor Hunter, Julie 334 Contributor Solle, Justin C 335 Contributor Murphy, Kaileigh 336 Contributor Nuytemans, Karen 337 Contributor Kieburtz, Karl 338 Contributor Lohmann, Katja 339 Contributor Marek, Kenneth 340 Contributor Mok, Kin Ying 341 Contributor Kumar, Kishore 342 Contributor Levine, Kristin 343 Contributor Chahine, Lana M 344 Contributor Lange, Lara M 345 Contributor Pihlstrøm, Lasse 346 Contributor Screven, Laurel 347 Contributor Stefanis, Leonidas 348 Contributor Shulman, Lisa 349 Contributor Marsili, Luca 350 Contributor Parnetti, Lucilla 351 Contributor Kuhl, Maggie 352 Contributor Funayama, Manabu 353 Contributor Sharma, Manu 354 Contributor Tan, Manuela 355 Contributor Kauffman, Marcelo 356 Contributor Miranda, Marcelo 357 Contributor Bustamante, Maria Leonor 358 Contributor Stamelou, Maria 359 Contributor Periñan Tocino, Maria Teresa 360 Contributor Cornejo-Olivas, Mario 361 Contributor Dean, Marissa 362 Contributor Jimenez Del Rio, Marlene 363 Contributor Makarious, Mary B 364 Contributor Atadzhanov, Masharip 365 Contributor Koretsky, Mathew 366 Contributor Rodriguez-Violante, Mayela 367 Contributor Ellis, Melina 368 Contributor Avenali, Micol 369 Contributor Rizig, Mie 370 Contributor Rentería, Miguel E 371 Contributor Inca-Martines, Miguel Z 372 Contributor Nalls, Mike A 373 Contributor Ibrahim Norlinah, Mohamed 374 Contributor Salama, Mohamed 375 Contributor Umair, Muhammad 376 Contributor Ip, Nancy 377 Contributor Louie, Naomi 378 Contributor Cheung, Nelson Yuk-Fai 379 Contributor Mencacci, Niccolò Emanuele 380 Contributor Wood, Nicholas 381 Contributor Williams, Nigel 382 Contributor Okubadejo, Njideka 383 Contributor Hattori, Nobutaka 384 Contributor Abdul Murad, Nor Azian 385 Contributor Ibrahim, Norlinah Mohamed 386 Contributor Okunoye, Olaitan 387 Contributor Ojo, Oluwadamilola 388 Contributor Monchi, Oury 389 Contributor Öztop Çakmak, Özgür 390 Contributor Öztop Çakmak, Patricio Öztop Çakmak 391 Contributor Lewis, Patrick Alfryn 392 Contributor Pastor, Pau 393 Contributor Reyes-Pérez, Paula 394 Contributor Saffie Awad, Paula 395 Contributor Chana, Pedro 396 Contributor Chan, Phillip 397 Contributor Kung, Pin-Jui 398 Contributor Chan, Piu 399 Contributor Pal, Pramod 400 Contributor Lingappa Kukkle, Prashanth 401 Contributor Ojha, Rajeev 402 Contributor Kaiyrzhanov, Rauan 403 Contributor Krüger, Rejko 404 Contributor Amouri, Rim 405 Contributor Weil, Rimona 406 Contributor Rajan, Roopa 407 Contributor Alcalay, Roy 408 Contributor Wu, Ruey-Meei 409 Contributor Borgohain, Rupam 410 Contributor Sassi, Samia Ben 411 Contributor Khachatryan, Samson 412 Contributor Bandres-Ciga, Sara 413 Contributor El-Sadig, Sarah 414 Contributor Wu, Serena 415 Contributor Groppa, Sergio 416 Contributor Azmin, Shahrul 417 Contributor Lim, Shen-Yang 418 Contributor Ur-Rehman, Shoaib 419 Contributor Ertan, Sibel 420 Contributor Stott, Simon 421 Contributor Jasaitye, Simona 422 Contributor Chowdhury, Sohini 423 Contributor Dumanis, Sonya 424 Contributor Bardien, Soraya 425 Contributor Lubbe, Steven 426 Contributor Koks, Sulev 427 Contributor Dey, Sumit 428 Contributor Xie, Tao 429 Contributor Foroud, Tatiana 430 Contributor Fon, Ted 431 Contributor Beach, Thomas 432 Contributor Gasser, Thomas 433 Contributor Anderson, Tim 434 Contributor Nguyen, Toan 435 Contributor Sherer, Todd 436 Contributor Schirinzi, Tommaso 437 Contributor Shiraishi, Tomotaka 438 Contributor Pitcher, Toni 439 Contributor Obese, Vida 440 Contributor Tumas, Vitor 441 Contributor Mohamed, Wael 442 Contributor Kamel, Walaa A 443 Contributor Luo, Wei 444 Contributor Zhou, Xiaopu 445 Contributor Zewde, Yared Z 446 Contributor Song, Yeajin 447 Contributor Wen, Yi 448 Contributor Wu, Yihru 449 Contributor Joong Kim, Yun 450 Contributor Tavadyan, Zaruhi 451 Contributor Fang, Zih-Hua 452 Contributor 10.1016/S1474-4422(23)00283-1 Vol. 22, no. 11, p. 1015 - 1025 PERI:(DE-600)2079704-7 11 1015 - 1025 The lancet 22 2023 1474-4422 http://pub.dzne.de/record/265764/files/DZNE-2023-01035_Restricted.pdf http://pub.dzne.de/record/265764/files/DZNE-2023-01035_Restricted.pdf?subformat=pdfa pdfa oai:pub.dzne.de:265764 VDB Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 42 P:(DE-2719)9001362 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-354 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Prevention and Healthy Aging 0 2023 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2023-08-24 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2023-08-24 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-10-24 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-10-24 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-10-24 DBCoverage StatID:(DE-HGF)1110 StatID Current Contents - Clinical Medicine 2023-10-24 JCR StatID:(DE-HGF)0100 StatID LANCET NEUROL : 2022 2023-10-24 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-10-24 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2023-10-24 Peer Review StatID:(DE-HGF)0030 StatID ASC 2023-10-24 IF >= 40 StatID:(DE-HGF)9940 StatID LANCET NEUROL : 2022 2023-10-24 I:(DE-2719)1210002 AG Heutink Genome Biology of Neurodegenerative Diseases 0 journal VDB I:(DE-2719)1210002 UNRESTRICTED