Biology subjects

Cornejo-Olivas, M.

Publications and source records attributed to Cornejo-Olivas, M..

4 recordsLinked to original sources

bioRxiv2025

Multi-ancestry Transcriptome-Wide Association Study Reveals Shared and Population-Specific Genetic Effects in Alzheimer's Disease

Alzheimers disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA-seq and genotype data from NHW (n=235), African American (AA; n=224), and Hispanic (HISP; n=292) MAGENTA participants. Using SuShiE for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (FDR<0.05, PIP>0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the GWAS index SNP rs6733839 (r2 {approx} 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.

genomics↗

bioRxiv2024

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

genomics↗

bioRxiv2020

Dissecting the role of Amerindian genetic ancestry and ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population

Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. ApoE {varepsilon}4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic White populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in{varepsilon} 4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to [~]80 of Amerindian ancestry provides a unique opportunity to assess the role of Amerindian ancestry in Alzheimer disease. In this study we assess the effect of the ApoE {varepsilon}4 allele on AD in the Peruvian population. A total of 78 AD cases and 128 unrelated cognitive healthy controls were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE {varepsilon}4 allele on Alzheimer disease was tested using a logistic regression model by adjusting for age, gender, and population substructure (first three principal components). Logistic regression results showed that ApoE {varepsilon}4 allele is significantly associated with AD in Peruvian population with the high-risk effect (OR = 5.02, CI: 2.3-12.5, p-value = 2e-4). The average values of the local ancestries surrounding the ApoE gene (chr19:44Mb-46Mb) have the highest proportion of Amerindian (60.6%), followed by European (33.9%) and African (5.5%) ancestral backgrounds. Our results showed that the risk for AD from ApoE {varepsilon}4 in Peruvians is higher than we have observed in non-Hispanic White populations. Given the high admixture of Amerindian ancestry in the Peruvian population, it suggests that the Amerindian local ancestry is contributing to a strong risk for AD in ApoE {varepsilon}4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE {varepsilon}4 and the ancestral backgrounds located around the genomic region of ApoE gene.

genetics↗

bioRxiv2019

Guillain-Barre syndrome outbreak in Peru: Association with polymorphisms in IL-17, ICAM-1 and CD1

Guillain-Barre Syndrome (GBS) is considered a complex disorder with significant environmental effect and genetic susceptibility. Genetic polymorphisms in CD1E, CD1A, IL-17 and/or ICAM-1 genes had been proposed as susceptibility genetic variants for GBS mainly in Caucasian population. This study explores the association between selected polymorphisms in these genes and GBS susceptibility in confirmed GBS cases reported in mestizo population from northern Peru during the most recent GBS outbreak of May 2018. A total of 9 non-related cases and 11 controls were sequenced for the polymorphic regions of CD1A, CD1E, IL-17 and ICAM-1 genes. We found a significant protective association between heterozygous GA genotype in ICAM-1 gene (241Gly / Arg) and GBS (p <0.047). IL-17 was monomorphic in both controls and patients. No significant differences were found in the frequency of SNPs in CD1A and CD1E between the group with GBS patients and healthy controls. Further studies with larger sample size will be required to validate these findings.

molecular biology↗