Polygenic risk and pleiotropy in neurodegenerative diseases

被引：33

作者：

Bellou, Eftychia ^{[1
]}

Stevenson-Hoare, Joshua ^{[1
]}

Escott-Price, Valentina ^{[1
]}

机构：

[1] Cardiff Univ, Dementia Res Inst, Hadyn Ellis Bldg,Maindy Rd, Cardiff CF24 4HQ, Wales

来源：

NEUROBIOLOGY OF DISEASE | 2020年 / 142卷

基金：

英国医学研究理事会; “创新英国”项目;

关键词：

Polygenic risk score; Pleiotropy; Heritability; Neurodegenerative disease; AMYOTROPHIC-LATERAL-SCLEROSIS; GENOME-WIDE ASSOCIATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; GENETIC ARCHITECTURE; COMPLEX DISEASES; SCORE ANALYSIS; HERITABILITY; METAANALYSIS; INSIGHTS;

D O I：

10.1016/j.nbd.2020.104953

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

In this paper we explore the phenomenon of pleiotropy in neurodegenerative diseases, focusing on Alzheimer's disease (AD). We summarize the various techniques developed to investigate pleiotropy among traits, elaborating in the polygenic risk scores (PRS) analysis. PRS was designed to assess a cumulative effect of a large number of SNPs for association with a disease and, later for disease risk prediction. Since genetic predictions rely on heritability, we discuss SNP-based heritability from genome-wide association studies and its contribution to the prediction accuracy of PRS. We review work examining pleiotropy in neurodegenerative diseases and related phenotypes and biomarkers. We conclude that the exploitation of pleiotropy may aid in the identification of novel genes and provide further insights in the disease mechanisms, and along with PRS analysis, may be advantageous for precision medicine.

引用

页数：7

共 96 条

[41] Medicine - The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics [J].

Hardy, J ;

Selkoe, DJ .

SCIENCE, 2002, 297 (5580) :353-356

[42] Evolvability and Neurodegenerative Disease: Antagonistic Pleiotropy Phenomena Derived from Amyloid Aggregates [J].

Hashimoto, Makoto ;

Ho, Gilbert ;

Takamatsu, Yoshiki ;

Shimizu, Yuka ;

Sugama, Shuei ;

Takenouchi, Takato ;

Waragai, Masaaki ;

Masliah, Eliezer .

JOURNAL OF PARKINSONS DISEASE, 2018, 8 (03) :405-408

[43] Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders [J].

Hill, W. David ;

Davies, Gail ;

Liewald, David C. ;

McIntosh, Andrew M. ;

Deary, Ian J. .

BIOLOGICAL PSYCHIATRY, 2016, 80 (04) :266-273

[44] Polygenic Risk Scores in Neurodegenerative Diseases: a Review [J].

Ibanez, Laura ;

Farias, Fabiana H. G. ;

Dube, Umber ;

Mihindukulasuriya, Kathie A. ;

Harari, Oscar .

CURRENT GENETIC MEDICINE REPORTS, 2019, 7 (01) :22-29

[45] Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels [J].

Ibanez, Laura ;

Dube, Umber ;

Saef, Benjamin ;

Budde, John ;

Black, Kathleen ;

Medvedeva, Alexandra ;

Del-Aguila, Jorge L. ;

Davis, Albert A. ;

Perlmutter, Joel S. ;

Harari, Oscar ;

Benitez, Bruno A. ;

Cruchaga, Carlos .

BMC NEUROLOGY, 2017, 17

[46] Tau-tubulin kinase [J].

Ikezu, Seiko ;

Ikezu, Tsuneya .

FRONTIERS IN MOLECULAR NEUROSCIENCE, 2014, 7

[47] Serial PIB and MRI in normal, mild cognitive impairment and Alzheimers disease: implications for sequence of pathological events in Alzheimers disease [J].

Jack, Clifford R., Jr. ;

Lowe, Val J. ;

Weigand, Stephen D. ;

Wiste, Heather J. ;

Senjem, Matthew L. ;

Knopman, David S. ;

Shiung, Maria M. ;

Gunter, Jeffrey L. ;

Boeve, Bradley F. ;

Kemp, Bradley J. ;

Weiner, Michael ;

Petersen, Ronald C. .

BRAIN, 2009, 132 :1355-1365

[48] Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer's disease risk [J].

Jansen, Iris E. ;

Savage, Jeanne E. ;

Watanabe, Kyoko ;

Bryois, Julien ;

Williams, Dylan M. ;

Steinberg, Stacy ;

Sealock, Julia ;

Karlsson, Ida K. ;

Hagg, Sara ;

Athanasiu, Lavinia ;

Voyle, Nicola ;

Proitsi, Petroula ;

Witoelar, Aree ;

Stringer, Sven ;

Aarsland, Dag ;

Almdahl, Ina S. ;

Andersen, Fred ;

Bergh, Sverre ;

Bettella, Francesco ;

Bjornsson, Sigurbjorn ;

Braekhus, Anne ;

Brathen, Geir ;

de Leeuw, Christiaan ;

Desikan, Rahul S. ;

Djurovic, Srdjan ;

Dumitrescu, Logan ;

Fladby, Tormod ;

Hohman, Timothy J. ;

Jonsson, Palmi, V ;

Kiddle, Steven J. ;

Rongve, Arvid ;

Saltvedt, Ingvild ;

Sando, Sigrid B. ;

Selbaek, Geir ;

Shoai, Maryam ;

Skene, Nathan G. ;

Snaedal, Jon ;

Stordal, Eystein ;

Ulstein, Ingun D. ;

Wang, Yunpeng ;

White, Linda R. ;

Hardy, John ;

Hjerling-Leffler, Jens ;

Sullivan, Patrick F. ;

van der Flier, Wiesje M. ;

Dobson, Richard ;

Davis, Lea K. ;

Stefansson, Hreinn ;

Stefansson, Kari ;

Pedersen, Nancy L. .

NATURE GENETICS, 2019, 51 (03) :404-+

[49] The prevalence and incidence of dementia with Lewy bodies: a systematic review of population and clinical studies [J].

Jones, S. A. Vann ;

O'Brien, J. T. .

PSYCHOLOGICAL MEDICINE, 2014, 44 (04) :673-683

[50] A novel Alzheimer disease locus located near the gene encoding tau protein [J].

Jun, G. ;

Ibrahim-Verbaas, C. A. ;

Vronskaya, M. ;

Lambert, J-C ;

Chung, J. ;

Naj, A. C. ;

Kunkle, B. W. ;

Wang, L-S ;

Bis, J. C. ;

Bellenguez, C. ;

Harold, D. ;

Lunetta, K. L. ;

Destefano, A. L. ;

Grenier-Boley, B. ;

Sims, R. ;

Beecham, G. W. ;

Smith, A. V. ;

Chouraki, V. ;

Hamilton-Nelson, K. L. ;

Ikram, M. A. ;

Fievet, N. ;

Denning, N. ;

Martin, E. R. ;

Schmidt, H. ;

Kamatani, Y. ;

Dunstan, M. L. ;

Valladares, O. ;

Laza, A. R. ;

Zelenika, D. ;

Ramirez, A. ;

Foroud, T. M. ;

Choi, S-H ;

Boland, A. ;

Becker, T. ;

Kukull, W. A. ;

van der Lee, S. J. ;

Pasquier, F. ;

Cruchaga, C. ;

Beekly, D. ;

Fitzpatrick, A. L. ;

Hanon, O. ;

Gill, M. ;

Barber, R. ;

Gudnason, V. ;

Campion, D. ;

Love, S. ;

Bennett, D. A. ;

Amin, N. ;

Berr, C. ;

Tsolaki, Magda .

MOLECULAR PSYCHIATRY, 2016, 21 (01) :108-117

← 1 2 3 4 5 6 7 8 9 10 →