In:
Alzheimer's & Dementia, Wiley, Vol. 16, No. S3 ( 2020-12)
Abstract:
Despite several genetic variants identified by large genetic studies, late‐onset Alzheimer’s disease and related dementias (ADRD)’s missing heritability remains extensive. Aging has accelerated globally and over 70% of the elderly population reside in developing countries; by 2050 people with dementia in Latin America is projected to increase 4‐fold. Hispanics are the largest ethnic minority in the US, and have a unique genetic background characterized by admixture of various proportions of European, African, and Native‐American ancestry. Although studies have reported higher incidence and prevalence of ADRD in Hispanics, there are limited investigations on the effect of ancestry on ADRD, in particular Native‐American ancestry. Method The analysis sample consisted of 1,702 Mexicans from urban and rural areas, part of the national sample of the Mexican Health and Aging Study (MHAS) for whom genotyping array, sociodemographic and clinical data were available (128 cases, 524 mild cognitive impairment [MCI], 1050 controls; 57% female; age 60‐98). Estimated proportions of European, African, and Native American ancestries were employed as predictors in regression and survival models (3‐year follow‐up) to study their associations with risk of ADRD or conversion from cognitively normal to MCI or ADRD. Result The MHAS sample exhibited a large Native‐American component (63%) followed by European (33%) and African (4%) (N = 1,702; Figure 1, right panel). For comparison purposes, we show Mexicans from the 1000genomes project (N = 66; Figure 1, left panel) which exhibited a larger European component (48%), and lower Native‐American component (48%). Regression analyses showed Native‐American ancestry to be significantly associated with higher risk of ADRD (OR = 1.19, 95%CI: 1.12‐1.28). Native ancestry also significantly predicted conversion from cognitively intact status to MCI or ADRD (HR = 1.11, 95%CI: 1‐1.24). APOE‐e4 was not associated with ADRD (OR = 1.5, p‐value = 0.720) Conclusion The MHAS provides a true representation of the genetic landscape of Mexico yielding a Native‐American enriched cohort, compared to small, geographically‐limited studies such as the 1000 genomes project. Native‐American ancestry increases the risk for ADRD and might explain the observed higher frequency of ADRD among Hispanic populations. Lastly, we confirmed lack of association for APOE as previously reported in smaller investigations.
Type of Medium:
Online Resource
ISSN:
1552-5260
,
1552-5279
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
2201940-6
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