Browsing by Author "Gonzalez, Christian"

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    Allostatic load calculation in a Chilean older-adults cohort reveals the need for age-specific clinical thresholds
    (2025) Buller, Ingrid; Muniz, Graciela; Lillo, Patricia; Riquelme, Patricio; Demanet, Michele; Saguez, Rodrigo; Damm, Francisca; Salech, Felipe; Gonzalez, Christian; Court, Felipe; Thumala, Daniela; Slachevsky Chonchol, Andrea
    Only few studies of Allostatic Load (AL) have been conducted in Latin-American cohorts. Here, we replicated a recently proposed comprehensive algorithm (ALCS) to derive an AL index in a Chilean cohort of cognitive healthy adults. Using data from the GERO cohort (n = 166, age 76.92 ± 5.07 years) we generated an ALCS AL index through and compared for model fit with a purely sample distribution l algorithm (ALES). ALCS largely improved when some clinical values were corrected for ages ≥65, although failed to achieve sufficient goodness of fit. A final inclusion of an additional inflammatory biomarker resulted in further improvement of ALES, but not on ALCS. The ALES algorithm, which do not include clinical thresholds, achieved satisfactory fit after correcting for sample disparities between sexes. This suggests the need to consider the suitability of clinical thresholds developed in younger populations and the need to develop specific thresholds for assessing older adults.
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    The first genome-wide association study in the Argentinian and Chilean populations identifies shared genetics with Europeans in Alzheimer's disease
    (2024) Dalmasso, Maria; De Rojas, Itziar; Olivar, Natividad; Muchnik, Carolina; Angel, Bárbara; Gloger, Sergio; Sanchez, Mariana; Chacón, María; Aránguiz, Rafael; Orellana, Paulina; Cuesta, Carolina; Galeano, Pablo; Campanelli, Lorenzo; Novack, Gisela; Martinez, Luis; Medel, Nancy; Lisso, Julieta; Sevillano, Zulma; Irureta, Nicolás; Castaño, Eduardo; Montrreal, Laura; Thoenes, Michaela; Hanses, Claudia; Heilmann-Heimbach, Stefanie; Kairiyama, Claudia; Mintz, Inés; Villella, Ivana; Rueda, Fabiana; Romero, Amanda; Wukitsevits, Nancy; Quiroga, Ivana; Gona, Cristian; Lamber, Jean-Charles; Solis, Patricia; Politis, Daniel; Mangone, Carlos; Gonzalez, Christian; Boada, Mercè; Tàrraga, Lluís; Slachevsky Chonchol, Andrea
    Introduction: Genome-wide association studies (GWAS) are fundamental for identifying loci associated with diseases. However, they require replication in other ethnicities. Methods: We performed GWAS on sporadic Alzheimer's disease (AD) including 539 patients and 854 controls from Argentina and Chile. We combined our results with those from the European Alzheimer and Dementia Biobank (EADB) in a meta-analysis and tested their genetic risk score (GRS) performance in this admixed population. Results: We detected apolipoprotein E ε4 as the single genome-wide significant signal (odds ratio = 2.93 [2.37-3.63], P = 2.6 × 10-23 ). The meta-analysis with EADB summary statistics revealed four new loci reaching GWAS significance. Functional annotations of these loci implicated endosome/lysosomal function. Finally, the AD-GRS presented a similar performance in these populations, despite the score diminished when the Native American ancestry rose. Discussion: We report the first GWAS on AD in a population from South America. It shows shared genetics modulating AD risk between the European and these admixed populations. Highlights: This is the first genome-wide association study on Alzheimer's disease (AD) in a population sample from Argentina and Chile. Trans-ethnic meta-analysis reveals four new loci involving lysosomal function in AD. This is the first independent replication for TREM2L, IGH-gene-cluster, and ADAM17 loci. A genetic risk score (GRS) developed in Europeans performed well in this population. The higher the Native American ancestry the lower the GRS values

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