Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry

被引：6

作者：

Ray, Nicholas R. ^{[1
]}

Kunkle, Brian W. ^{[2
]}

Hamilton-Nelson, Kara ^{[2
]}

Kurup, Jiji T. ^{[1
]}

Rajabli, Farid ^{[2
]}

Qiao, Min ^{[1
]}

Vardarajan, Badri N. ^{[1
]}

Cosacak, Mehmet I. ^{[3
]}

Kizil, Caghan ^{[1
]}

Jean-Francois, Melissa ^{[2
]}

Cuccaro, Michael ^{[2
]}

Reyes-Dumeyer, Dolly ^{[1
]}

Cantwell, Laura ^{[4
]}

Kuzma, Amanda ^{[4
]}

Vance, Jeffery M. ^{[2
]}

Gao, Sujuan ^{[5
]}

Hendrie, Hugh C. ^{[6
]}

Baiyewu, Olusegun ^{[7
]}

Ogunniyi, Adesola ^{[7
]}

Akinyemi, Rufus O. ^{[7
]}

Lee, Wan-Ping ^{[4
]}

Martin, Eden R. ^{[2
,8
]}

Wang, Li-San ^{[4
]}

Beecham, Gary W. ^{[2
]}

Bush, William S. ^{[9
,10
,11
]}

Xu, Wanying ^{[9
]}

Jin, Fulai ^{[9
,10
,11
]}

Wang, Liyong ^{[2
]}

Farrer, Lindsay A. ^{[12
,13
,14
,15
,16
]}

Haines, Jonathan L. ^{[10
,11
]}

Byrd, Goldie S. ^{[17
]}

Schellenberg, Gerard D. ^{[4
]}

Mayeux, Richard ^{[1
,18
,19
,20
,21
]}

Pericak-Vance, Margaret A. ^{[2
]}

Reitz, Christiane ^{[1
,18
,19
,21
]}

机构：

[1] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA

[2] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA

[3] German Ctr Neurodegenerat Dis, Dresden, Germany

[4] Univ Penn, Perelman Sch Med, Penn Neurodegenerat Genom Ctr, Dept Pathol & Lab Med, Philadelphia, PA USA

[5] Indiana Univ Sch Med, Dept Biostat & Hlth Data Sci, Indianapolis, IN USA

[6] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN USA

[7] Univ Ibadan, Coll Med, Ibadan, Oyo, Nigeria

[8] Univ Miami, Dr John T MacDonald Fdn, Dept Human Genet, Miami, FL USA

[9] Case Western Reserve Univ, Sch Med, Dept Genet & Genome Sci, Biomed Res, Cleveland, OH USA

[10] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland, OH USA

[11] Case Western Reserve Univ, Cleveland Inst Computat Biol, Sch Med, Cleveland, OH USA

[12] Boston Univ, Sch Med, Dept Med, Biomed Genet Sect, Boston, MA USA

[13] Boston Univ, Sch Med, Dept Neurol, Boston, MA USA

[14] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[15] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA USA

[16] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[17] Wake Forest Sch Med, Maya Angelou Ctr Hlth Equ, Winston Salem, NC USA

[18] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA

[19] Columbia Univ, Dept Neurol, New York, NY USA

[20] Columbia Univ, Dept Psychiat, New York, NY USA

[21] Columbia Univ, Coll Phys & Surg, Epidemiol, New York, NY USA

来源：

ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 08期

基金：

加拿大健康研究院; 美国国家卫生研究院; 英国医学研究理事会; 英国惠康基金;

关键词：

African Americans; African genome Panel; Alzheimer's disease; genome-wide association study; RISK LOCI; METAANALYSIS; SRGAP3; EXPRESSION; IMPUTATION; COMPLEXES; DIAGNOSIS; EPSILON-4; VARIANTS; DEMENTIA;

D O I：

10.1002/alz.13880

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, P = 3.68x10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9x10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects.

引用

页码：5247 / 5261

页数：15

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