Phenotype harmonization and analysis for The Populations Underrepresented in Mental illness Association Studies (the PUMAS Project).

Autor:	Ramirez-Diaz AM; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Diaz-Zuluaga AM; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Stroud RE 2nd; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Vreeker A; Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands.; Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Rotterdam, The Netherlands., Bitta M; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.; Department of Psychiatry, University of Oxford, Oxford, UK., Ivankovic F; Analytic and Translational Genetics Unit, Massachusetts General Hospital Research Institute, Richard B. Simches Research Building, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Wootton O; Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa., Whiteman CA; Robert Wood Johnson Medical School, Rutgers University, New Brunswick, USA., Mountcastle H; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Jha SC; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Georgakopoulos P; Center for Psychiatric Health and Genomics, Rutgers University, New Brunswick, USA., Kaur I; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Mena L; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Asaaf S; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., de Souza Rodrigues AL; Universidade do Estado do Para, Belém, Brazil.; Hospital de Clinicas Gaspar Vianna, Belém, Brazil.; Centro Universitario do Para, Belém, Brazil., Ziebold C; Federal University of São Paulo - UNIFESP, Department of Psychiatry, São Paulo, Brazil., Newton CRJC; Department of Psychiatry, University of Oxford, Oxford, UK.; Neurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya.; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa., Stein DJ; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.; SA MRC Unit on Risk & Resilience in Mental Disorders, University of Cape Town and Neuroscience Institute, Cape Town, South Africa., Akena D; Department of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda., Valencia-Echeverry J; Research Group in Psychiatry (GIPSI), Department of Psychiatry, School of Medicine, Universidad de Antioquia, Medellin, Colombia., Kyebuzibwa J; Department of Psychiatry, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda., Palacio-Ortiz JD; Research Group in Psychiatry (GIPSI), Department of Psychiatry, School of Medicine, Universidad de Antioquia, Medellin, Colombia., McMahon J; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Ongeri L; Center for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya., Chibnik LB; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA., Quarantini LC; Universidade Federal da Bahia (UFBA), Salvador, Brazil., Atwoli L; Department of Mental Health and Behavioural Sciences, School of Medicine, Moi University College of Health Sciences, Eldoret, Kenya.; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya., Santoro ML; Disciplina de Biologia Molecular, Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil.; Laboratory of Integrative Neuroscience (LiNC), Universidade Federal de São Paulo, São Paulo, Brazil., Baker M; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA., Diniz MJA; Pax Instituto de Psiquiatria, Goiânia, Brazil., Castaño-Ramirez M; Department of Mental Health and Human Behavior, Universidad de Caldas, Manizales, Colombia., Alemayehu M; Department of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia., Holanda N; Hospital de Saúde Mental Professor Frota Pinto (HSMM), Fortaleza, Brazil., Ayola-Serrano NC; CEMIC Mental Health Clinic, Cartagena, Colombia., Lorencetti PG; Laboratory of Integrative Neuroscience (LiNC), Universidade Federal de São Paulo, São Paulo, Brazil., Mwema RM; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya., James R; Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa., Albuquerque S; Hospital de Saúde Mental Professor Frota Pinto (HSMM), Fortaleza, Brazil., Sharma S; Center for Psychiatric Health and Genomics, Rutgers University, New Brunswick, USA., Chapman SB; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital Research Institute, Richard B. Simches Research Building, Boston, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA., Belangero SI; Laboratory of Integrative Neuroscience (LiNC), Universidade Federal de São Paulo, São Paulo, Brazil.; Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo,, Brazil., Teferra S; Department of Psychiatry, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia., Gichuru S; Department of Mental Health, Moi Teaching and Referral Hospital, Eldoret, Kenya., Service SK; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Kariuki SM; Neurosciences Unit, Clinical Department, KEMRI-Wellcome Trust Research Programme-Coast, Kilifi, Kenya.; Department of Psychiatry, University of Oxford, Oxford, UK., Freitas TH; Federal University of São Paulo - UNIFESP, Department of Psychiatry, São Paulo, Brazil.; University of Fortaleza - UNIFOR, Faculty of Medicine, Fortaleza, Brazil., Zingela Z; Executive Dean's Office, Faculty of Health Sciences, Nelson Mandela University, Gqebera, South Africa., Gadelha A; Federal University of São Paulo - UNIFESP, Department of Psychiatry, São Paulo, Brazil., Bearden CE; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA.; Department of Psychology, University of California Los Angeles, Los Angeles, USA., Ophoff RA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA.; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA., Neale BM; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital Research Institute, Richard B. Simches Research Building, Boston, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA., Martin AR; Analytic and Translational Genetics Unit, Massachusetts General Hospital Research Institute, Richard B. Simches Research Building, Boston, USA.; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA., Koenen KC; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA.; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, USA., Pato CN; Center for Psychiatric Health and Genomics, Rutgers University, New Brunswick, USA., Lopez-Jaramillo C; Research Group in Psychiatry (GIPSI), Department of Psychiatry, School of Medicine, Universidad de Antioquia, Medellin, Colombia., Reus V; Department of Psychiatry and Behavioral Sciences, UCSF School of Medicine, UCSF Weill Institute for Neurosciences, San Francisco, USA., Freimer N; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA., Pato MT; Center for Psychiatric Health and Genomics, Rutgers University, New Brunswick, USA., Gelaye B; Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA., Loohuis LO; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, USA.; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.; Department of Computational Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, USA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 Oct 04. Date of Electronic Publication: 2024 Oct 04.
DOI:	10.1101/2024.10.02.24314732
Abstrakt:	Background: The Populations Underrepresented in Mental illness Association Studies (PUMAS) project is attempting to remediate the historical underrepresentation of African and Latin American populations in psychiatric genetics through large-scale genetic association studies of individuals diagnosed with a serious mental illness [SMI, including schizophrenia (SCZ), schizoaffective disorder (SZA) bipolar disorder (BP), and severe major depressive disorder (MDD)] and matched controls. Given growing evidence indicating substantial symptomatic and genetic overlap between these diagnoses, we sought to enable transdiagnostic genetic analyses of PUMAS data by conducting phenotype alignment and harmonization for 89,320 participants (48,165 cases and 41,155 controls) from four cohorts, each of which used different ascertainment and assessment methods: PAISA n=9,105; PUMAS-LATAM n=14,638; NGAP n=42,953 and GPC n=22,624. As we describe here, these efforts have yielded harmonized datasets enabling us to analyze PUMAS genetic variation data at three levels: SMI overall, diagnoses, and individual symptoms. Methods: In aligning item-level phenotypes obtained from 14 different clinical instruments, we incorporated content, branching nature, and time frame for each phenotype; standardized diagnoses; and selected 19 core SMI item-level phenotypes for analyses. The harmonization was evaluated in PUMAS cases using multiple correspondence analysis (MCA), co-occurrence analyses, and item-level endorsement. Outcomes: We mapped >6,895 item-level phenotypes in the aggregated PUMAS data, in which SCZ (44.97%) and severe BP (BP-I, 31.53%) were the most common diagnoses. Twelve of the 19 core item-level phenotypes occurred at frequencies of > 10% across all diagnoses, indicating their potential utility for transdiagnostic genetic analyses. MCA of the 14 phenotypes that were present for all cohorts revealed consistency across cohorts, and placed MDD and SCZ into separate clusters, while other diagnoses showed no significant phenotypic clustering. Interpretation: Our alignment strategy effectively aggregated extensive phenotypic data obtained using diverse assessment tools. The MCA yielded dimensional scores which we will use for genetic analyses along with the item level phenotypes. After successful harmonization, residual phenotypic heterogeneity between cohorts reflects differences in branching structure of diagnostic instruments, recruitment strategies, and symptom interpretation (due to cultural variation).
Databáze:	MEDLINE
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