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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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.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>Using DNA extracted from this community-based diverse cohort (<i>N</i> = 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.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Genotype frequencies for 12 out of 15 SNPs (2 apolipoprotein E [<i>APOE</i>] variants<i>, SIPA1L2, PIK3C2G, GPC6, RBFOX1, ABCA7, VRK3, ALCAM, EDEM1, NSG/MSX2</i>, and <i>WDR70)</i> differed significantly between groups.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Alzheimer's disease (AD) burden is rapidly increasing in the United States; minorities are disproportionally affected.</li>\n \n <li>We investigate genetic health disparities in our community-based diverse cohort.</li>\n \n <li>Twelve of 15 evaluated single nucleotide polymorphisms significantly differ among ethnicities in the Health & Aging Brain Study–Health Disparities.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 2","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70124","citationCount":"0","resultStr":"{\"title\":\"Alzheimer's disease genetic risk: Top African American risk allele frequencies and genetic architecture among Mexican-, African-, and non-Hispanic White Americans\",\"authors\":\"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\",\"doi\":\"10.1002/trc2.70124\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>Using DNA extracted from this community-based diverse cohort (<i>N</i> = 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. 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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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Alzheimer's disease (AD) burden is rapidly increasing in the United States; minorities are disproportionally affected.</li>\\n \\n <li>We investigate genetic health disparities in our community-based diverse cohort.</li>\\n \\n <li>Twelve of 15 evaluated single nucleotide polymorphisms significantly differ among ethnicities in the Health & Aging Brain Study–Health Disparities.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":53225,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"volume\":\"11 2\",\"pages\":\"\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/trc2.70124\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70124\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70124","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Alzheimer's disease genetic risk: Top African American risk allele frequencies and genetic architecture among Mexican-, African-, and non-Hispanic White Americans
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.
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.
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