Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

NEUROBIOLOGY OF AGING

卷:38

Article

Guerreiro, Rita¹  Escott-Price, Valentina²  Darwent, Lee¹  Parkkinen, Laura³  Ansorge, Olaf³  Hernandez, Dena G.^4,5  Nalls, Michael A.⁴  Clark, Lorraine^6,7  Honig, Lawrence^6,7  Marder, Karen^6,8  van der Flier, Wiesje^9,10  Holstege, Henne^9,10  Louwersheimer, Eva^9,10  Lemstra, Afina^9,10  Scheltens, Philip^9,10  Rogaeva, Ekaterina¹¹  St George-Hyslop, Peter^11,12,13  Londos, Elisabet¹⁴  Zetterberg, Henrik^1,15  Ortega-Cubero, Sara^16,17  Pastor, Pau^16,17,18,19  Ferman, Tanis J.^20,21  Graff-Radford, Neill R.²²  Ross, Owen A.²³  Barber, Imelda²⁴  Braae, Anne²⁴  Brown, Kristelle²⁴  Morgan, Kevin²⁴  Maetzler, Walter^25,26  Berg, Daniela^25,26  Troakes, Claire²⁷  Al-Sarraj, Safa²⁷  Lashley, Tammaryn²⁸  Compta, Yaroslau^28,29  Revesz, Tamas²⁸  Lees, Andrew²⁸  Cairns, Nigel J.³⁰  Halliday, Glenda M.^31,32  Mann, David³³  Pickering-Brown, Stuart³³  Powell, John³⁴  Lunnon, Katie³⁵  Lupton, Michelle K.³⁴  Dickson, Dennis²³  Hardy, John³⁶  Singleton, Andrew⁴  Bras, Jose¹ 

[1] UCL, Inst Neurol, Dept Mol Neurosci, 8-11 Queen Sq,DRC,Box 16, London WC1N 3AR, England

[2] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Gen, Cardiff CF10 3AX, S Glam, Wales

[3] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford Parkinsons Dis Ctr, Oxford, England

[4] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA

[5] German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany

[6] Columbia Univ, Taub Inst Alzheimer Dis & Aging Brain, New York, NY USA

[7] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA

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

[9] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[10] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[11] Univ Toronto, Dept Med, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada

[12] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England

[13] Univ Cambridge, Cambridge Natl Inst Hlth Res, Biomed Res Unit Dementia, Cambridge, England

[14] Lund Univ, Inst Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden

[15] Univ Gothenburg, Clin Neurochem Lab, Dept Psychiat & Neurochem, Inst Neurosci & Physiol,Sahlgrenska Acad, Gothenburg, Sweden

[16] Univ Navarra, Ctr Appl Med Res CIMA, Div Neurosci, Neurogenet Lab, E-31080 Pamplona, Spain

[17] Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Madrid, Spain

[18] Univ Barcelona, Sch Med, Memory Unit, Dept Neurol,Univ Hosp Mutua Terrassa, Barcelona, Spain

[19] Univ Barcelona, Sch Med, Movement Disorders Unit, Dept Neurol,Univ Hosp Mutua Terrassa, Barcelona, Spain

[20] Mayo Clin, Dept Psychiat, Jacksonville, FL 32224 USA

[21] Mayo Clin, Dept Psychol, Jacksonville, FL 32224 USA

[22] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA

[23] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA

[24] Univ Nottingham, Translat Cell Sci Human Genet, Sch Life Sci, Queens Med Ctr, Nottingham NG7 2RD, England

[25] Univ Tubingen, Ctr Neurol, Dept Neurodegenerat, Hertie Inst Clin Brain Res, Tubingen, Germany

[26] German Ctr Neurodegenerat Dis, DZNE, Tubingen, Germany

[27] Kings Coll London, Dept Clin Neurosci, Inst Psychiat, MRC London Neurodegenerat Dis Brain Bank, London, England

[28] UCL Inst Neurol, Dept Mol Neurosci, Queen Sq Brain Bank, London, England

[29] Hosp Clin Univ Barcelona IDIBAPS, Clin Neurosci Inst ICN, Neurol Serv, Parkinsons Dis & Movement Disorders Unit, Barcelona, Spain

[30] Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA

[31] Neurosci Res Australia, Sydney, NSW, Australia

[32] Univ New S Wales, Fac Med, Sch Med Sci, Sydney, NSW, Australia

[33] Univ Manchester, Fac Med & Human Sci, Inst Brain Behav & Mental Hlth, Manchester, Lancs, England

[34] Kings Coll London, Dept Basic & Clin Neurosci, Inst Psychiat Psychol & Neurosci, London, England

[35] Univ Exeter, Univ Exeter Med Sch, Inst Clin & Biomed Sci, Exeter, Devon, England

[36] UCL Inst Neurol, Dept Mol Neurosci, Reta Lila Weston Res Labs, London, England

关键词: Dementia with Lewy bodies;    Alzheimer's disease;    Parkinson's disease;    Genetic correlation;   

DOI  :  10.1016/j.neurobiolaging.2015.10.028

来源: Elsevier

【 摘 要 】

The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. (C) 2016 The Authors. Published by Elsevier Inc.

【 授权许可】

Free