scholarly journals Admixture mapping reveals the association between Native American ancestry at 3q13.11 and reduced risk of Alzheimer’s disease in Caribbean Hispanics

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Andréa R. V. R. Horimoto ◽  
Diane Xue ◽  
Timothy A. Thornton ◽  
Elizabeth E. Blue
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Native American ◽  
Late Onset ◽  
European Ancestry ◽  
Admixture Mapping ◽  
Native American Ancestry ◽  
Genome Wide ◽  
A Genome ◽  
The Brain

Abstract Background Genetic studies have primarily been conducted in European ancestry populations, identifying dozens of loci associated with late-onset Alzheimer’s disease (AD). However, much of AD’s heritability remains unexplained; as the prevalence of AD varies across populations, the genetic architecture of the disease may also vary by population with the presence of novel variants or loci. Methods We conducted genome-wide analyses of AD in a sample of 2565 Caribbean Hispanics to better understand the genetic contribution to AD in this population. Statistical analysis included both admixture mapping and association testing. Evidence for differential gene expression within regions of interest was collected from independent transcriptomic studies comparing AD cases and controls in samples with primarily European ancestry. Results Our genome-wide association study of AD identified no loci reaching genome-wide significance. However, a genome-wide admixture mapping analysis that tests for association between a haplotype’s ancestral origin and AD status detected a genome-wide significant association with chromosome 3q13.11 (103.7–107.7Mb, P = 8.76E−07), driven by a protective effect conferred by the Native American ancestry (OR = 0.58, 95%CI = 0.47−0.73). Within this region, two variants were significantly associated with AD after accounting for the number of independent tests (rs12494162, P = 2.33E−06; rs1731642, P = 6.36E−05). The significant admixture mapping signal is composed of 15 haplotype blocks spanning 5 protein-coding genes (ALCAM, BBX, CBLB, CCDC54, CD47) and four brain-derived topologically associated domains, and includes markers significantly associated with the expression of ALCAM, BBX, CBLB, and CD47 in the brain. ALCAM and BBX were also significantly differentially expressed in the brain between AD cases and controls with European ancestry. Conclusion These results provide multiethnic evidence for a relationship between AD and multiple genes at 3q13.11 and illustrate the utility of leveraging genetic ancestry diversity via admixture mapping for new insights into AD.

scholarly journals A genome-wide association study for late-onset Alzheimer's disease using DNA pooling

2008 ◽  
Vol 1 (1) ◽  
Author(s):  
Richard Abraham ◽  
Valentina Moskvina ◽  
Rebecca Sims ◽  
Paul Hollingworth ◽  
Angharad Morgan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Genome Wide Association ◽  
Dna Pooling ◽  
Genome Wide ◽  
A Genome

A genome-wide association study of late-onset Alzheimer’s disease in a Japanese population

2015 ◽  
Vol 25 (4) ◽  
pp. 139-146 ◽  
Author(s):  
Atsushi Hirano ◽  
Tomoyuki Ohara ◽  
Atsushi Takahashi ◽  
Masayuki Aoki ◽  
Yuta Fuyuno ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

P3-196: A genome-wide association study for late-onset Alzheimer's disease using DNA pooling

2008 ◽  
Vol 4 ◽  
pp. T578-T578 ◽  
Author(s):  
Richard Abraham ◽  
Lyudmila Georgieva ◽  
Rebecca Sims ◽  
Angharad Morgan ◽  
Paul Hollingworth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
Genome Wide Association ◽  
Dna Pooling ◽  
Genome Wide ◽  
A Genome

Association of GWAS Top Genes With Late-Onset Alzheimer’s Disease in Colombian Population

2017 ◽  
Vol 32 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Diana Jennifer Moreno ◽  
Susana Ruiz ◽  
Ángela Ríos ◽  
Francisco Lopera ◽  
Henry Ostos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
European Ancestry ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms ◽  
Significant Interaction Effect ◽  
Single Nucleotide ◽  
Genome Wide

Objective: The association of variants in CLU, CR1, PICALM, BIN1, ABCA7, and CD33 genes with late-onset Alzheimer’s disease (LOAD) was evaluated and confirmed through genome-wide association study. However, it is unknown whether these associations can be replicated in admixed populations. Methods: The association of 14 single-nucleotide polymorphisms in those genes was evaluated in 280 LOAD cases and 357 controls from the Colombian population. Results: In a multivariate analysis using age, gender, APOE∊4 status, and admixture covariates, significant associations were obtained ( P < .05) for variants in BIN1 (rs744373, odds ratio [OR]: 1.42), CLU (rs11136000, OR: 0.66), PICALM (rs541458, OR: 0.69), ABCA7 (rs3764650, OR: 1.7), and CD33 (rs3865444, OR: 1.12). Likewise, a significant interaction effect was observed between CLU and CR1 variants with APOE. Conclusion: This study replicated the associations previously reported in populations of European ancestry and shows that APOE variants have a regulatory role on the effect that variants in other loci have on LOAD, reflecting the importance of gene–gene interactions in the etiology of neurodegenerative diseases.

scholarly journals Potential Novel Genes for Late-Onset Alzheimer’s Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study

2021 ◽  
pp. 1-10
Author(s):  
Sarang Kang ◽  
Jungsoo Gim ◽  
Jiwoon Lee ◽  
Tamil Iniyan Gunasekaran ◽  
Kyu Yeong Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Late Onset ◽  
East Asian ◽  
Genome Wide Association ◽  
Japanese Cohort ◽  
Genome Wide ◽  
A Genome

The present study reports two novel genome-wide significant loci for late-onset Alzheimer’s disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer’s disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer’ and Related Dementias (GARD) cohort study. The study was replicated in a Japanese cohort of 1,956 subjects that suggested two novel susceptible SNPs in two genes: LRIG1 and CACNA1A. This study demonstrates that the discovery of AD-associated variants is feasible in non-European ethnic groups using samples comprising fewer subjects from the more homogeneous genetic background.

scholarly journals 5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Lei Chen ◽  
Qianqian Shen ◽  
Shunliang Xu ◽  
Hongzhuan Yu ◽  
Shengjie Pei ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Late Onset ◽  
Critical Role ◽  
Cell Free Dna ◽  
Free Dna ◽  
Genome Wide ◽  
A Genome ◽  
Normal Controls ◽  
Circulating Cell Free Dna

Background: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in central nervous system. It has been reported that DNA 5hmC dysregulation play a critical role in Alzheimer’s disease (AD) pathology. Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. Objective: However, the genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD has not been reported to date. Methods: We carried out a case-control study and used a genome-wide chemical capture followed by high-throughput sequencing to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in late-onset AD patients and the control. Results: We discovered significant differences of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls, indicating they can be well distinguished from normal controls by DhMRs in cfDNA. Specially, we identified 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) with predicting diagnostic potential based on their significant correlations with MMSE and MoCA scores of subjects. Conclusion: The present results suggest that 5hmC markers derived from plasma cfDNA can served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD.

scholarly journals Common variants inABCG8andTRAF3genes confer risk for gallstone disease and gallbladder cancer in admixed Latinos with Mapuche Native American ancestry

2018 ◽  
Author(s):  
Bernabé I. Bustos ◽  
Eduardo Pérez-Palma ◽  
Stephan Buch ◽  
Lorena Azócar ◽  
Eleodoro Riveras ◽  
...  
Keyword(s):  
Native American ◽  
Gallbladder Cancer ◽  
Cholesterol Gallstone ◽  
Gallstone Disease ◽  
Population Attributable Risk ◽  
European Ancestry ◽  
Expression Levels ◽  
Native American Ancestry ◽  
Genome Wide ◽  
A Genome

BackgroundLatin Americans and Chilean Amerindians have the highest prevalence of cholesterol gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however they only explain a small portion of the population-attributable risk of the disease.MethodsWe performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Latinos with Mapuche Native American Ancestry, followed by a replication analysis of 10 candidate single nucleotide polymorphisms (SNPs) with suggestive genome-wide significance (P<1×10−5) in 1,643 individuals. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Logistic regression analyses were adjusted for age, sex, BMI, Type 2 Diabetes and Amerindian ancestry. Associated variants were further examined in two large GSD European populations and in a Chilean gallbladder cancer (GBC) cohort. We determined the expression levels of a novel GSD-candidate gene in normal and GSD-tissue samples.ResultsWe consistently replicated theABCG8gene (rs11887534; P=3.24×10−8, OR=1.74) associated with GSD in admixed Latinos and identified a novel candidate signal within theTRAF3gene on chromosome 14 (rs12882491; P=1.11×10−7, OR=1.40).ABCG8andTRAF3variants also conferred risk to GBC. Gene expression analyses indicated thatTRAF3levels were significantly decreased in the gallbladder (P=0.015) and the duodenal mucosa (P=0.001) of affected GSD individuals compared to healthy controls.ConclusionsWe confirmedABCG8and identifiedTRAF3both associated with GSD and GBC in admixed Latinos. Decreased TRAF3 expression levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

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