Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease

被引：4

作者：

Archer, Derek B. ^{[1
,2
]}

Eissman, Jaclyn M. ^{[1
,2
]}

Mukherjee, Shubhabrata ^{[3
]}

Lee, Michael L. ^{[3
]}

Choi, Seo-Eun ^{[3
]}

Scollard, Phoebe ^{[3
]}

Trittschuh, Emily H. ^{[4
,5
]}

Mez, Jesse B. ^{[6
]}

Bush, William S. ^{[7
]}

Kunkle, BrianW. ^{[8
]}

Naj, Adam C. ^{[9
,10
]}

Gifford, Katherine A. ^{[1
]}

Cuccaro, Michael L. ^{[8
]}

Pericak-Vance, Margaret A. ^{[8
]}

Farrer, Lindsay A. ^{[6
,11
,12
]}

Wang, Li-San ^{[10
]}

Schellenberg, Gerard D. ^{[10
]}

Mayeux, Richard P. ^{[13
,14
,15
,16
]}

Haines, Jonathan L. ^{[7
]}

Jefferson, Angela L. ^{[1
]}

Kukull, Walter A. ^{[17
]}

Keene, C. Dirk ^{[18
]}

Saykin, Andrew J. ^{[19
,20
,21
]}

Thompson, Paul M. ^{[22
]}

Martin, Eden R. ^{[8
]}

Bennett, David A. ^{[23
]}

Barnes, Lisa L. ^{[23
]}

Schneider, Julie A. ^{[23
]}

Crane, Paul K. ^{[3
]}

Dumitrescu, Logan ^{[1
,2
]}

Hohman, Timothy J. ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Vanderbilt Memory & Alzheimers Ctr, 1207 17th Ave S, Nashville, TN 37212 USA

[2] Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA

[3] Univ Washington, Dept Med, Seattle, WA USA

[4] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA

[5] GRECC, VA Puget Sound Hlth Care Syst, Seattle, WA USA

[6] Boston Univ, Chobanian & Avedisian Sch Med, Dept Neurol, Boston, MA 02215 USA

[7] Case Western Reserve Univ, Dept Populat & Quantitat Hlth Sci, Cleveland Inst Computat Biol, Cleveland, OH 44106 USA

[8] Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA

[9] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA

[10] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Penn Neurodegenerat Genom Ctr, Philadelphia, PA 19104 USA

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

[12] Boston Univ, Chobanian & Avedisian Sch Med, Dept Med Biomed Genet, Boston, MA 02215 USA

[13] Columbia Univ, New York, NY USA

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

[15] Columbia Univ, Med Ctr, Inst Genom Med, New York, NY USA

[16] New York Presbyterian Hosp, New York, NY USA

[17] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA

[18] Univ Washington, Dept Lab Med & Pathol, Seattle, WA 98195 USA

[19] Indiana Univ Sch Med, Dept Radiol & Imaging Serv, Indianapolis, IN 46202 USA

[20] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN USA

[21] Indiana Univ Sch Med, Indiana Alzheimers Dis Res Ctr, Indianapolis, IN 46202 USA

[22] Univ Southern Calif, Keck Sch Med, Stevens Neuroimaging & Informat Inst, Imaging Genet Ctr, Marina Del Rey, CA USA

[23] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

来源：

ALZHEIMERS & DEMENTIA | 2024年 / 20卷 / 02期

关键词：

Alzheimer's disease; genetics; GWAS; memory; GENOME-WIDE ASSOCIATION; GENERAL COGNITIVE FUNCTION; CENTER NACC DATABASE; RISK LOCI; METAANALYSIS; PATHWAYS; REVEALS;

D O I：

10.1002/alz.13508

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

INTRODUCTION: Although large-scale genome-wide association studies (GWAS) have been conducted on AD, few have been conducted on continuous measures of memory performance andmemory decline. METHODS: We conducted a cross-ancestry GWAS on memory performance (in 27,633 participants) and memory decline (in 22,365 participants; 129,201 observations) by leveraging harmonized cognitive data from four aging cohorts. RESULTS: We found high heritability for two ancestry backgrounds. Further, we found a novel ancestry locus for memory decline on chromosome 4 (rs6848524) and three loci in the non-Hispanic Black ancestry group for memory performance on chromosomes 2 (rs111471504), 7 (rs4142249), and 15 (rs74381744). In our gene-level analysis, we found novel genes for memory decline on chromosomes 1 (SLC25A44), 11 (BSX), and 15 (DPP8). Memory performance and memory decline shared genetic architecture with AD-related traits, neuropsychiatric traits, and autoimmune traits. DISCUSSION: We discovered several novel loci, genes, and genetic correlations associated with late-lifememory performance and decline.

引用

页码：1268 / 1283

页数：16

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