Alzheimer's disease genetic risk: Top African American risk allele frequencies and genetic architecture among Mexican-, African-, and non-Hispanic White Americans

IF 4.9 Q1 CLINICAL NEUROLOGY

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Pub Date : 2025-06-19 DOI:10.1002/trc2.70124

Mohammad Housini, Zhengyang Zhou, Lubnaa Abdullah, Gita Pathak, Reem Ayoub, John Gutierrez, Shea Andrews, Nicole Phillips, Sid O'Bryant, Robert Barber, For the HABS-HD Study Team

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Abstract

INTRODUCTION

Alzheimer's disease (AD) continues to be the sixth leading cause of death in the United States. Significant efforts are spent researching etiology and potential management strategies. Although minorities face a higher disease burden and are anticipated to make up 43% of the US population by 2060, most literature on inherited AD risk has been derived from studying European ancestry. Here we evaluate frequencies of top AD risk alleles for late-onset AD (LOAD) in African- (AA), Mexican- (MA) and non-Hispanic White (NHW)-American participants enrolled in the Health & Aging Brain Study–Health Disparities (HABS-HD) cohort to determine ethnicity-specific differential genetic architecture.

METHODS

Using DNA extracted from this community-based diverse cohort (N = 3207), we calculated the genotype frequencies in each population to determine whether a significant difference is detected among the three populations. DNA genotyping was performed per manufacturer's protocols. Imputation was used for single nucleotide polymorphisms (SNPs) that were not directly genotyped. Statistical analysis was performed using R Studio.

RESULTS

Genotype frequencies for 12 out of 15 SNPs (2 apolipoprotein E [APOE] variants, SIPA1L2, PIK3C2G, GPC6, RBFOX1, ABCA7, VRK3, ALCAM, EDEM1, NSG/MSX2, and WDR70) differed significantly between groups.

DISCUSSION

This analysis expands on our previous study supporting the notion that genetic risk for AD is heterogeneous across racial and ethnic populations. Our results continue to demonstrate the valuable nature of diversity in genetic risk investigations and suggest the importance of including diverse and underrepresented racial and ethnic populations in medical research. Perhaps the most interesting finding is observed in the SNPs not found to be significantly different between groups, indicating there may be shared pleiotropic gene architecture across ethnicities.

Highlights

Alzheimer's disease (AD) burden is rapidly increasing in the United States; minorities are disproportionally affected.
We investigate genetic health disparities in our community-based diverse cohort.
Twelve of 15 evaluated single nucleotide polymorphisms significantly differ among ethnicities in the Health & Aging Brain Study–Health Disparities.

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阿尔茨海默病的遗传风险：墨西哥裔、非洲裔和非西班牙裔美国白人中最高的非裔美国人风险等位基因频率和遗传结构

阿尔茨海默病（AD）仍然是美国第六大死亡原因。研究病因和潜在的治疗策略花费了大量的精力。尽管少数民族面临着更高的疾病负担，预计到2060年将占美国人口的43%，但大多数关于遗传性AD风险的文献都来自对欧洲血统的研究。在这里，我们评估了非洲裔（AA）、墨西哥裔（MA）和非西班牙裔白人（NHW）美国参与者中迟发性AD （LOAD）的顶级AD风险等位基因的频率。衰老脑研究-健康差异（HABS-HD）队列确定种族特异性差异遗传结构。方法使用从社区多样化队列（N = 3207）中提取的DNA，计算每个人群的基因型频率，以确定三个人群之间是否存在显著差异。按照制造商的方案进行DNA基因分型。非直接基因分型的单核苷酸多态性（snp）采用归算方法。使用R Studio进行统计分析。结果15个snp中有12个（载脂蛋白E [APOE] 2个变异、SIPA1L2、PIK3C2G、GPC6、RBFOX1、ABCA7、VRK3、ALCAM、EDEM1、NSG/MSX2和WDR70）的基因型频率在组间差异显著。该分析扩展了我们之前的研究，该研究支持阿尔茨海默病的遗传风险在种族和民族人群中是异质的这一概念。我们的研究结果继续证明了遗传风险调查中多样性的宝贵性质，并建议在医学研究中包括多样化和代表性不足的种族和族裔人口的重要性。也许最有趣的发现是在群体之间没有发现显著差异的snp，这表明不同种族之间可能存在共同的多效性基因结构。在美国，阿尔茨海默病（AD）负担正在迅速增加；少数族裔受到的影响尤为严重。我们在以社区为基础的多样化队列中调查遗传健康差异。15个被评估的单核苷酸多态性中有12个在种族间存在显著差异。衰老大脑研究——健康差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer''s and Dementia: Translational Research and Clinical Interventions Medicine-Psychiatry and Mental Health

CiteScore

10.10

自引率

2.10%

发文量

134

审稿时长

10 weeks

期刊介绍： Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.