Global and local ancestry in African‐Americans: Implications for Alzheimer's disease risk

Abstract

African American (AA) individuals have a higher risk for late-onset Alzheimer’s disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the AD-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. Exploratory post-hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

“…Next, our study was dominated by samples of European ancestry. Racial and ethnic differences in AD prevalence and genetics are recognized in the literature 1,[47][48][49] . Although FBAT is robust to confounding due to population structure, an expanded set of underrepresented populations is necessary to identify AD sex-specific effects unique to other populations.…”

Neuropathologic differences by race from the National Alzheimer's Coordinating Center

“…History of hypertension, diabetes, heart attack, atrial fibrillation, stroke, hypercholesterolemia, parkinsonism, and years smoking was obtained from report by the participant and/or co-participant at the most recent UDS visit. Body mass index (kg/m 2 ) was calculated from height and weight measured at the most recent UDS visit using the standardized calculation[36], and was categorized as <25kg/m 2 (underweight or normal weight); 25–29.9 kg/m 2 (overweight), and ≥30 kg/m 2 (obese). Systolic and diastolic blood pressure were measured at the most recent UDS visit.…”

Dementia and Alzheimer's disease risks in patients with autoimmune disorders

“…Even for vascular dementia, controversy over the exact nature of the relationship between cerebrovascular pathology and cognitive impairment exists . Evidence from epidemiological, neuroimaging and neuropathological research supports the role of educational level, genetic, vascular and psychosocial factors in the development of Alzheimer's disease . Genetic susceptibility has been proven to play a role in the development of Alzheimer's disease.…”

“…3 Evidence from epidemiological, neuroimaging and neuropathological research supports the role of educational level, genetic, vascular and psychosocial factors in the development of Alzheimer's disease. [4][5][6][7][8][9][10] Genetic susceptibility has been proven to play a role in the development of Alzheimer's disease. Early-onset familial Alzheimer's disease is often caused by autosomal dominant mutations, which account for approximately just 2-5% of all patients with Alzheimer's disease.…”