Sex-specific genetic architecture of late-life memory performance

被引：0

作者：

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

Archer, Derek B. ^{[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, Brian W. ^{[8
]}

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

Gifford, Katherine A. ^{[1
]}

Cuccaro, Michael L. ^{[8
]}

Cruchaga, Carlos ^{[11
,12
]}

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

Farrer, Lindsay A. ^{[6
,13
,14
]}

Wang, Li-San ^{[10
]}

Schellenberg, Gerard D. ^{[10
]}

Mayeux, Richard P. ^{[15
,16
,17
,18
]}

Haines, Jonathan L. ^{[7
]}

Jefferson, Angela L. ^{[1
]}

Kukull, Walter A. ^{[19
]}

Keene, C. Dirk ^{[20
]}

Saykin, Andrew J. ^{[21
,22
]}

Thompson, Paul M. ^{[23
]}

Martin, Eden R. ^{[8
]}

Bennett, David A. ^{[24
]}

Barnes, Lisa L. ^{[24
]}

Schneider, Julie A. ^{[24
]}

Crane, Paul K. ^{[3
]}

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

Dumitrescu, Logan ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Vanderbilt Memory & Alzheimers Ctr, Nashville, TN 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, Cleveland Inst Computat Biol, Dept Populat & Quantitat Hlth Sci, 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] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[12] Washington Univ, Sch Med, NeuroGen & Informat Ctr, St Louis, MO USA

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

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

[15] Columbia Univ, New York, NY USA

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

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

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

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

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

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

[22] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[23] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90007 USA

[24] 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：

aging; Alzheimer's disease; endophenotypes; cognition; Genomics; GWAS; memory; sex differences; sex-specific; CENTER NACC DATABASE; HEPARAN-SULFATE; COGNITIVE-ABILITIES; EPISODIC MEMORY; ALZHEIMERS; HERITABILITY; IQCJ-SCHIP1; EXPRESSION; EXCRETION; VARIANTS;

D O I：

暂无

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

BACKGROUND: Women demonstrate a memory advantage when cognitively healthy yet lose this advantage to men in Alzheimer's disease. However, the genetic underpinnings of this sex difference inmemory performance remain unclear. METHODS: We conducted the largest sex-aware genetic study on late-lifememory to date (N-males = 11,942; N-females = 15,641). Leveraging harmonized memory composite scores from four cohorts of cognitive aging and AD, we performed sex-stratified and sex-interaction genome-wide association studies in 24,216 non-Hispanic White and 3367 non-Hispanic Black participants. RESULTS: We identified three sex-specific loci (rs67099044-CBLN2, rs719070-SCHIP1/IQCJ-SCHIP), including an X-chromosome locus (rs5935633EGL6/TCEANC/OFD1), that associated with memory. Additionally, we identified heparan sulfate signaling as a sex-specific pathway and found sex-specific genetic correlations between memory and cardiovascular, immune, and education traits. DISCUSSION: This study showed memory is highly and comparably heritable across sexes, as well as highlighted novel sex-specific genes, pathways, and genetic correlations that related to late-life memory.

引用

页码：1250 / 1267

页数：18

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