Browsing by Author "Lopera, Francisco"

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    Biomarkers for dementia in Latin American countries: Gaps and opportunities
    (2023) Parra, Mario A.; Orellana, Paulina; Leon, Tomas; Victoria, Cabello G.; Henriquez, Fernando; Gomez, Rodrigo; Avalos, Constanza; Damian, Andres; Slachevsky, Andrea; Ibanez, Agustin; Zetterberg, Henrik; Tijms, Betty M.; Yokoyama, Jennifer S.; Pina-Escudero, Stefanie D.; Cochran, J. Nicholas; Matallana, Diana L.; Acosta, Daisy; Allegri, Ricardo; Arias-Suarez, Bianca P.; Barra, Bernardo; Behrens, Maria Isabel; Brucki, SoniaM. D.; Busatto, Geraldo; Caramelli, Paulo; Castro-Suarez, Sheila; Contreras, Valeria; Custodio, Nilton; Dansilio, Sergio; De la Cruz-Puebla, Myriam; de Souza, Leonardo Cruz; Diaz, Monica M.; Duque, Lissette; Farias, Gonzalo A.; Ferreira, Sergio T.; Guimet, Nahuel Magrath; Kmaid, Ana; Lira, David; Lopera, Francisco; Meza, Beatriz Mar; Miotto, Eliane C.; Nitrini, Ricardo; Nunez, Alberto; O'Neill, Santiago; Ochoa, John; Pintado-Caipa, Maritza; Resende, Elisa de Paula Franca; Risacher, Shannon; Rojas, Luz Angela; Sabaj, Valentina; Schilling, Lucas; Sellek, Allis F.; Sosa, Ana; Takada, Leonel T.; Teixeira, Antonio L.; Unaucho-Pilalumbo, Martha; Duran-Aniotz, Claudia
    Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC) countries remains a serious barrier. Here, we reported a survey to explore the ongoing work, needs, interests, potential barriers, and opportunities for future studies related to biomarkers. The results show that neuroimaging is the most used biomarker (73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cerebrospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears to undermine the implementation of biomarkers in clinical or research settings, followed by insufficient infrastructure and training. The survey revealed that despite the above barriers, the region holds a great potential to advance dementia biomarkers research. Considering the unique contributions that LAC could make to this growing field, we highlight the urgent need to expand biomarker research. These insights allowed us to propose an action plan that addresses the recommendations for a biomarker framework recently proposed by regional experts.
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    Mutations in sphingolipid metabolism genes are associated with ADHD
    (2020) Henriquez-Henriquez, Marcela; Acosta, Maria T.; Martinez, Ariel F.; Velez, Jorge, I; Lopera, Francisco; Pineda, David; Palacio, Juan D.; Quiroga, Teresa; Worgall, Tilla S.; Deckelbaum, Richard J.; Mastronardi, Claudio; Molina, Brooke S. G.; Arcos-Burgos, Mauricio; Muenke, Maximilian
    Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC,CERS6,SMPD1,SMPDL3B,CERS2,FADS3,ELOVL5, andCERK). Successful local replication for associations with variants inGALC,SMPD1, andCERS6was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increasedGALCexpression in the cerebellum.