Sofia Moura, Luciana Bertholim Nasciben, Aura M. Ramirez, Lauren Coombs, Joe Rivero, Derek J. Van Booven, Brooke A. DeRosa, Kara L. Hamilton-Nelson, Patrice L. Whitehead, Larry D. Adams, Takiyah D. Starks, Pedro R. Mena, Maryenela Illanes-Manrique, Sergio Tejada, Goldie S. Byrd, Mario R. Cornejo-Olivas, Briseida E. Feliciano-Astacio, Karen Nuytemans, Liyong Wang, Margaret A. Pericak-Vance, Derek M. Dykxhoorn, Farid Rajabli, Anthony J. Griswold, Juan I. Young, Jeffery M. Vance
{"title":"Comparing Alzheimer's genes in African, European, and Amerindian induced pluripotent stem cell–derived microglia","authors":"Sofia Moura, Luciana Bertholim Nasciben, Aura M. Ramirez, Lauren Coombs, Joe Rivero, Derek J. Van Booven, Brooke A. DeRosa, Kara L. Hamilton-Nelson, Patrice L. Whitehead, Larry D. Adams, Takiyah D. Starks, Pedro R. Mena, Maryenela Illanes-Manrique, Sergio Tejada, Goldie S. Byrd, Mario R. Cornejo-Olivas, Briseida E. Feliciano-Astacio, Karen Nuytemans, Liyong Wang, Margaret A. Pericak-Vance, Derek M. Dykxhoorn, Farid Rajabli, Anthony J. Griswold, Juan I. Young, Jeffery M. Vance","doi":"10.1002/alz.70031","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Genome-wide association studies (GWAS) studies in Alzheimer's disease (AD) demonstrate ancestry-specific loci. Previous studies in the regulatory architecture have only been conducted in Europeans (EUs), thus studies in additional ancestries are needed. Given the prevalence of AD genes expressed in microglia, we initiated our studies in induced pluripotent stem cell (iPSC) -derived microglia.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We created iPSC-derived microglia from 13 individuals of either high Amerindian (AI), African (AF), or EU global ancestry, including both AD and controls. RNA-seq, ATAC-seq, and pathway analyses were compared between ancestries in both AD and non-AD genes.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Twelve AD genes were differentially expressed genes (DEGs) and/or accessible between ancestries, including <i>ABI3</i>, <i>CTSB</i>, and <i>MS4A6A</i>. A total of 5% of all genes had differential ancestral expression, but differences in accessibility were less than 1%. The DEGs were enriched in known AD pathways.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>This resource will be valuable in evaluating AD in admixed populations and other neurological disorders and understanding the AD risk differences between populations.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>First comparison of the genomics of AI, AF, and EU microglia.</li>\n \n <li>Report differences in expression and accessibility of AD genes between ancestries.</li>\n \n <li>Ancestral expression differences are greater than differences in accessibility.</li>\n \n <li>Good transcriptome correlation was seen between brain and iPSC-derived microglia.</li>\n \n <li>Differentially expressed AD genes were in known AD pathways.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70031","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/alz.70031","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
INTRODUCTION
Genome-wide association studies (GWAS) studies in Alzheimer's disease (AD) demonstrate ancestry-specific loci. Previous studies in the regulatory architecture have only been conducted in Europeans (EUs), thus studies in additional ancestries are needed. Given the prevalence of AD genes expressed in microglia, we initiated our studies in induced pluripotent stem cell (iPSC) -derived microglia.
METHODS
We created iPSC-derived microglia from 13 individuals of either high Amerindian (AI), African (AF), or EU global ancestry, including both AD and controls. RNA-seq, ATAC-seq, and pathway analyses were compared between ancestries in both AD and non-AD genes.
RESULTS
Twelve AD genes were differentially expressed genes (DEGs) and/or accessible between ancestries, including ABI3, CTSB, and MS4A6A. A total of 5% of all genes had differential ancestral expression, but differences in accessibility were less than 1%. The DEGs were enriched in known AD pathways.
DISCUSSION
This resource will be valuable in evaluating AD in admixed populations and other neurological disorders and understanding the AD risk differences between populations.
Highlights
First comparison of the genomics of AI, AF, and EU microglia.
Report differences in expression and accessibility of AD genes between ancestries.
Ancestral expression differences are greater than differences in accessibility.
Good transcriptome correlation was seen between brain and iPSC-derived microglia.
Differentially expressed AD genes were in known AD pathways.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
