Genome-wide association analysis of cognitive function in Danish long-lived individuals

被引：4

作者：

Nygaard, Marianne ^{[1
,2
,3
]}

Dowsett, Joseph ^{[1
,2
,4
]}

McGue, Matt ^{[1
,2
,5
]}

Christensen, Kaare ^{[1
,2
,3
,6
]}

Christiansen, Lene ^{[1
,2
,4
]}

Tan, Qihua ^{[1
,2
,3
]}

Mengel-From, Jonas ^{[1
,2
,3
]}

机构：

[1] Univ Southern Denmark, Danish Twin Registry, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark

[2] Univ Southern Denmark, Danish Aging Res Ctr, Dept Publ Hlth, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark

[3] Odense Univ Hosp, Dept Clin Genet, JB Winsloews Vej 4, DK-5000 Odense C, Denmark

[4] Copenhagen Univ Hosp, Rigshosp, Dept Clin Immunol, Blegdamsvej 9, DK-2100 Copenhagen OE, Denmark

[5] Univ Minnesota, Dept Psychol, 75 East River Rd, Minneapolis, MN 55455 USA

[6] Odense Univ Hosp, Dept Clin Biochem & Pharmacol, Klovervaenget 47, DK-5000 Odense C, Denmark

来源：

MECHANISMS OF AGEING AND DEVELOPMENT | 2021年 / 195卷

关键词：

Cognitive function; Long-lived individuals; Genome-wide association study; Gene-based analysis; Pathway analysis; ALZHEIMERS-DISEASE; COHORTS BORN; METAANALYSIS; LOCI; HERITABILITY; EXPRESSION; GENE; ABILITY; PLINK; OLDER;

D O I：

10.1016/j.mad.2021.111463

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cognitive function is a substantially heritable trait related to numerous important life outcomes. Several genomewide association studies of cognitive function have in recent years led to the identification of thousands of significantly associated loci and genes. Individuals included in these studies have rarely been nonagenarians and centenarians, and since cognitive function is an important component of quality of life for this rapidly expanding demographic group, there is a need to explore genetic factors associated with individual differences in cognitive function at advanced ages. In this study, we pursued this by performing a genome-wide association study of cognitive function in 490 long-lived Danes (age range 90.1-100.8 years). While no genome-wide significant SNPs were identified, suggestively significant SNPs (P < 1 x 10(-5)) were mapped to several interesting genes, including ZWINT, CELF2, and DNAH5, and the glutamate receptor genes GRID2 and GRM7. Additionally, results from a gene set overrepresentation analysis indicated potential roles of gene sets related to G protein-coupled receptor (GPCR) signaling, interaction between L1 and ankyrins, mitogen-activated protein kinase (MAPK) signaling, RNA degradation, and cell cycle. Larger studies are needed to shed further light on the possible importance of these suggestive genes and pathways in cognitive function in nonagenarians and centenarians.

引用

页数：9

共 63 条

[1] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[2] SELECTIVE EXPRESSION OF THE GLUTAMATE-RECEPTOR CHANNEL DELTA-2 SUBUNIT IN CEREBELLAR PURKINJE-CELLS [J].

ARAKI, K ;

MEGURO, H ;

KUSHIYA, E ;

TAKAYAMA, C ;

INOUE, Y ;

MISHINA, M .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 197 (03) :1267-1276

[3] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[4] Second-generation PLINK: rising to the challenge of larger and richer datasets [J].

Chang, Christopher C. ;

Chow, Carson C. ;

Tellier, Laurent C. A. M. ;

Vattikuti, Shashaank ;

Purcell, Shaun M. ;

Lee, James J. .

GIGASCIENCE, 2015, 4

[5] Exceptional longevity does not result in excessive levels of disability [J].

Christensen, Kaare ;

McGue, Matt ;

Petersen, Inge ;

Jeune, Bernard ;

Vaupel, James W. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (36) :13274-13279

[6] Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart [J].

Christensen, Kaare ;

Thinggaard, Mikael ;

Oksuzyan, Anna ;

Steenstrup, Troels ;

Andersen-Ranberg, Karen ;

Jeune, Bernard ;

McGue, Matt ;

Vaupel, James W. .

LANCET, 2013, 382 (9903) :1507-1513

[7] Genome-wide association study of cognitive functions and educational attainment in UK Biobank (N=112151) [J].

Davies, G. ;

Marioni, R. E. ;

Liewald, D. C. ;

Hill, W. D. ;

Hagenaars, S. P. ;

Harris, S. E. ;

Ritchie, S. J. ;

Luciano, M. ;

Fawns-Ritchie, C. ;

Lyall, D. ;

Cullen, B. ;

Cox, S. R. ;

Hayward, C. ;

Porteous, D. J. ;

Evans, J. ;

McIntosh, A. M. ;

Gallacher, J. ;

Craddock, N. ;

Pell, J. P. ;

Smith, D. J. ;

Gale, C. R. ;

Deary, I. J. .

MOLECULAR PSYCHIATRY, 2016, 21 (06) :758-767

[8] Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949) [J].

Davies, G. ;

Armstrong, N. ;

Bis, J. C. ;

Bressler, J. ;

Chouraki, V. ;

Giddaluru, S. ;

Hofer, E. ;

Ibrahim-Verbaas, C. A. ;

Kirin, M. ;

Lahti, J. ;

van der Lee, S. J. ;

Le Hellard, S. ;

Liu, T. ;

Marioni, R. E. ;

Oldmeadow, C. ;

Postmus, I. ;

Smith, A. V. ;

Smith, J. A. ;

Thalamuthu, A. ;

Thomson, R. ;

Vitart, V. ;

Wang, J. ;

Yu, L. ;

Zgaga, L. ;

Zhao, W. ;

Boxall, R. ;

Harris, S. E. ;

Hill, W. D. ;

Liewald, D. C. ;

Luciano, M. ;

Adams, H. ;

Ames, D. ;

Amin, N. ;

Amouyel, P. ;

Assareh, A. A. ;

Au, R. ;

Becker, J. T. ;

Beiser, A. ;

Berr, C. ;

Bertram, L. ;

Boerwinkle, E. ;

Buckley, B. M. ;

Campbell, H. ;

Corley, J. ;

De Jager, P. L. ;

Dufouil, C. ;

Eriksson, J. G. ;

Espeseth, T. ;

Faul, J. D. ;

Ford, I. .

MOLECULAR PSYCHIATRY, 2015, 20 (02) :183-192

[9] Genome-wide association studies establish that human intelligence is highly heritable and polygenic [J].

Davies, G. ;

Tenesa, A. ;

Payton, A. ;

Yang, J. ;

Harris, S. E. ;

Liewald, D. ;

Ke, X. ;

Le Hellard, S. ;

Christoforou, A. ;

Luciano, M. ;

McGhee, K. ;

Lopez, L. ;

Gow, A. J. ;

Corley, J. ;

Redmond, P. ;

Fox, H. C. ;

Haggarty, P. ;

Whalley, L. J. ;

McNeill, G. ;

Goddard, M. E. ;

Espeseth, T. ;

Lundervold, A. J. ;

Reinvang, I. ;

Pickles, A. ;

Steen, V. M. ;

Ollier, W. ;

Porteous, D. J. ;

Horan, M. ;

Starr, J. M. ;

Pendleton, N. ;

Visscher, P. M. ;

Deary, I. J. .

MOLECULAR PSYCHIATRY, 2011, 16 (10) :996-1005

[10] Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function [J].

Davies, Gail ;

Lam, Max ;

Harris, Sarah E. ;

Trampush, Joey W. ;

Luciano, Michelle ;

Hill, W. David ;

Hagenaars, Saskia P. ;

Ritchie, Stuart J. ;

Marioni, Riccardo E. ;

Fawns-Ritchie, Chloe ;

Liewald, David C. M. ;

Okely, Judith A. ;

Ahola-Olli, Ari V. ;

Barnes, Catriona L. K. ;

Bertram, Lars ;

Bis, Joshua C. ;

Burdick, Katherine E. ;

Christoforou, Andrea ;

DeRosse, Pamela ;

Djurovic, Srdjan ;

Espeseth, Thomas ;

Giakoumaki, Stella ;

Giddaluru, Sudheer ;

Gustavson, Daniel E. ;

Hayward, Caroline ;

Hofer, Edith ;

Ikram, M. Arfan ;

Karlsson, Robert ;

Knowles, Emma ;

Lahti, Jari ;

Leber, Markus ;

Li, Shuo ;

Mather, Karen A. ;

Melle, Ingrid ;

Morris, Derek ;

Oldmeadow, Christopher ;

Palviainen, Teemu ;

Payton, Antony ;

Pazoki, Raha ;

Petrovic, Katja ;

Reynolds, Chandra A. ;

Sargurupremraj, Muralidharan ;

Scholz, Markus ;

Smith, Jennifer A. ;

Smith, Albert V. ;

Terzikhan, Natalie ;

Thalamuthu, Anbupalam ;

Trompet, Stella ;

van der Lee, Sven J. ;

Ware, Erin B. .

NATURE COMMUNICATIONS, 2018, 9

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