| Title: |
A new risk locus on chromosome 1 is suggested by genome‐wide association study in Peruvians for Alzheimer disease |
| Authors: |
Akgun, Bilcag; Cornejo‐Olivas, Mario; Custodio, Nilton; Rajabli, Farid; Soto‐Añari, Marcio F.; Montesinos, Rosa; Yang, Zikun; Huaman, Basilio C.; Reyes‐Dumeyer, Dolly; Cedeno, Jeffrey A; Rivero, Joe; Mena, Pedro R.; Adams, Larry D.; Whitehead, Patrice; Hamilton‐Nelson, Kara L.; Rios‐Pinto, Julia; Medina‐Colque, Angel; Dalgard, Clifton L.; Isasi, Rosario; Cornejo‐Herrera, Ivan; Illanes‐Manrique, Maryenela; Ochoa‐Valle, Edward; Sarapura‐Castro, Elison; Mejía, Koni K.; Milla‐Neyra, Karina; Castro‐Suarez, Sheila; Martin, Eden R.; Griswold, Anthony J.; McInerney, Katalina; Cuccaro, Michael L.; Vance, Jeffery M.; Beecham, Gary W.; Pericak‐Vance, Margaret A.; Tosto, Giuseppe |
| Source: |
Alzheimer's & Dementia ; volume 19, issue S12 ; ISSN 1552-5260 1552-5279 |
| Publisher Information: |
Wiley |
| Publication Year: |
2023 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background Increasing ethnic/ancestral diversity in genetic studies is critical for defining the genetic architecture of Alzheimer disease (AD). Amerindian (AI) populations are substantially underrepresented in AD genetic studies. The Peruvian (PE) population, with up to ∼80% of AI ancestry, provides a unique opportunity to assess the role of AI ancestry in AD. We performed the first genome‐wide association study (GWAS) in the PE population to identify novel AD susceptibility loci and characterize known AD genetic risk loci. Method The PE dataset includes array‐genotype and phenotype data from 542 individuals (189 cases; 353 controls), imputed to the NHLBI TOPMedv5 haplotype reference panel. We used a generalized linear mixed‐model (SAIGE software) for the GWAS analysis. We analyzed two separate models; the first model accounted for sex, age, and population substructure, while the second model also included the dosage of APOEe4. In both models, we included a genetic relationship matrix as a random effect to account for any potential relatedness. To determine if the associations are specific to specific ancestries, we employed ancestry‐aware approaches using the RFMix software. Result APOE was significantly associated with AD with an effect size comparable to that found in non‐Hispanic white (NHW) populations (OR = 3.3(2.2‐4.8),pv = 8.0×10 −10 ). Two additional known AD loci, TREML2 (pv = 0.008) and CLU (pv = 0.012), showed nominal significance Variants at three additional loci reached suggestive significance (pv |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/alz.077859 |
| Availability: |
https://doi.org/10.1002/alz.077859 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.C418505D |
| Database: |
BASE |