Exploring effect of known Alzheimer disease genetic loci in the Peruvian population. (20th December 2022)

• Record Type: Journal Article
• Authors: Cornejo‐Olivas, Mario; Rajabli, Farid; Kushch, Nicholas A.; Mena, Pedro Ramon; Illanes‐Manrique, Maryenela; Adams, Larry D.; Whitehead, Patrice L.; Hamilton‐Nelson, Kara L.; Milla‐Neyra, Karina; Marca, Victoria; Sarapura‐Castro, Elison; Manrique‐Enciso, Carla; Mejía, Koni K.; Isasi, Rosario; Castro‐Suarez, Sheila; Araujo‐Aliaga, Ismael; Custodio, Nilton; Montesinos, Rosa; Griswold, Anthony J.; Dalgard, Clifton L.; Beecham, Gary W.; Cuccaro, Michael L.; Vance, Jeffery M.; Pericak‐Vance, Margaret A.
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 3
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.068028
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Native American populations are substantially underrepresented in Alzheimer disease (AD) genetic studies. The Peruvian (PE) population with up to ∼80 of Amerindian ancestry (AI) provides a unique opportunity to assess the role of AI ancestry in AD. We performed whole‐genome sequencing in PE case‐control study to assess the effect of the known AD loci in PE population. Methods: Whole‐genome sequencing was performed in 96 AD cases and 145 unrelated cognitive healthy controls from PE population. We calculated the global ancestry (principal components) using the EIGENSTRAT approach. We tested 21 AD lead variants from the recent large non‐Hispanic White (NHW) GWAS of AD (Kunkle et al. 2019). We performed association analyses using logistic regression model with accounting for age, gender, and population substructure (first three principal components). We used Bonferroni approach for multiple test correction. Results: Logistic regression analysis confirmed association of APOE with AD (rs429358, OR=3.6, CI:1.9‐7.0; pv < 8.4e‐05) in PE population. CLU loci (rs9331896, pv=9.3e‐04) passed the significance threshold after Bonferroni multiple test correction. Two AD loci demonstrated nominal associations (pv<0.05), which were EPHA1 (rs10808026, pv = 0.028), and FERMT1 (rs17125924, pv=0.022) loci. Conclusion: Our results showed that known AD APOE and CLU loci are significantly associated with AD in PE population. Some of the genes demonstrated suggestive associations, but further analysis with a larger sample size is on‐going to determine if these reflect true associations.