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

Rita Guerreiro; Valentina Escott-Price; Lee Darwent; Laura Parkkinen; Olaf Ansorge; Dena G Hernandez; Michael A Nalls; Lorraine Clark; Lawrence Honig; Karen Marder; Wiesje van der Flier; Henne Holstege; Eva Louwersheimer; Afina Lemstra; Philip Scheltens; Ekaterina Rogaeva; Peter St George-Hyslop; Elisabet Londos; Henrik Zetterberg; Sara Ortega-Cubero; Pau Pastor; Tanis J Ferman; Neill R Graff-Radford; Owen A Ross; Imelda Barber; Anne Braae; Kristelle Brown; Kevin Morgan; Walter Maetzler; Daniela Berg; Claire Troakes; Safa Al-Sarraj; Tammaryn Lashley; Yaroslau Compta; Tamas Revesz; Andrew Lees; Nigel J Cairns; Glenda M Halliday; David Mann; Stuart Pickering-Brown; John Powell; Katie Lunnon; Michelle K Lupton; International Parkinson's Disease Genomics Consortium (IPDGC); Dennis Dickson; John Hardy; Andrew Singleton; Jose Bras

doi:10.1016/j.neurobiolaging.2015.10.028

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

Neurobiol Aging. 2016 Feb:38:214.e7-214.e10. doi: 10.1016/j.neurobiolaging.2015.10.028. Epub 2015 Nov 2.

Authors

Rita Guerreiro¹, Valentina Escott-Price², Lee Darwent¹, Laura Parkkinen³, Olaf Ansorge³, Dena G Hernandez⁴, Michael A Nalls⁵, Lorraine Clark⁶, Lawrence Honig⁶, Karen Marder⁷, Wiesje van der Flier⁸, Henne Holstege⁸, Eva Louwersheimer⁸, Afina Lemstra⁸, Philip Scheltens⁸, Ekaterina Rogaeva⁹, Peter St George-Hyslop¹⁰, Elisabet Londos¹¹, Henrik Zetterberg¹², Sara Ortega-Cubero¹³, Pau Pastor¹⁴, Tanis J Ferman¹⁵, Neill R Graff-Radford¹⁶, Owen A Ross¹⁷, Imelda Barber¹⁸, Anne Braae¹⁸, Kristelle Brown¹⁸, Kevin Morgan¹⁸, Walter Maetzler¹⁹, Daniela Berg¹⁹, Claire Troakes²⁰, Safa Al-Sarraj²⁰, Tammaryn Lashley²¹, Yaroslau Compta²², Tamas Revesz²¹, Andrew Lees²¹, Nigel J Cairns²³, Glenda M Halliday²⁴, David Mann²⁵, Stuart Pickering-Brown²⁵, John Powell²⁶, Katie Lunnon²⁷, Michelle K Lupton²⁶; International Parkinson's Disease Genomics Consortium (IPDGC); Dennis Dickson¹⁷, John Hardy²⁸, Andrew Singleton⁵, Jose Bras²⁹

Affiliations

¹ Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
² MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
³ Nuffield Department of Clinical Neurosciences, Oxford Parkinson's Disease Centre, University of Oxford, Oxford, UK.
⁴ Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
⁵ Laboratory of Neurogenetics, National Institutes on Aging, NIH, Bethesda, MD, USA.
⁶ Taub Institute for Alzheimer Disease and the Aging Brain, Columbia University, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.
⁷ Taub Institute for Alzheimer Disease and the Aging Brain, Columbia University, New York, NY, USA; Department of Neurology, Columbia University, New York, NY, USA.
⁸ Department Of Neurology and Alzheimer Center, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, the Netherlands.
⁹ Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
¹⁰ Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada; Cambridge Institute for Medical Research, and Cambridge National Institute of Health Research Biomedical Research Unit in Dementia, University of Cambridge, Cambridge, UK.
¹¹ Clinical Memory Research Unit, Institute of Clinical Sciences Malmö, Lund University, Lund, Sweden.
¹² Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK.
¹³ Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, (CIMA), University of Navarra, Pamplona, Spain; CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain.
¹⁴ Neurogenetics Laboratory, Division of Neurosciences, Center for Applied Medical Research, (CIMA), University of Navarra, Pamplona, Spain; CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, Madrid, Spain; Memory and Movement Disorders Units, Department of Neurology, University Hospital Mutua de Terrassa, University of Barcelona School of Medicine, Terrassa, Barcelona, Spain.
¹⁵ Departments of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.
¹⁶ Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
¹⁷ Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
¹⁸ Translation Cell Sciences-Human Genetics, School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
¹⁹ Hertie Institute for Clinical Brain Research, Department of Neurodegeneration, Center of Neurology, University of Tuebingen, and DZNE, German Center for Neurodegenerative Diseases, Tuebingen, Germany.
²⁰ MRC London Neurodegenerative Diseases Brain Bank, Institute of Psychiatry, Department of Clinical Neuroscience, King's College London, London, UK.
²¹ Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
²² Queen Square Brain Bank, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Parkinson's Disease & Movement Disorders Unit, Neurology Service, Clinical Neuroscience Institute (ICN), Hospital Clínic/University of Barcelona/IDIBAPS, Barcelona, Spain.
²³ Department of Neurology, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, Saint Louis, MO, USA.
²⁴ Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
²⁵ Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
²⁶ Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
²⁷ Institute of Clinical and Biomedical Science, University of Exeter Medical School, University of Exeter, Exeter, UK.
²⁸ Reta Lila Weston Research Laboratories, Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
²⁹ Department of Molecular Neuroscience, Institute of Neurology, UCL, London, UK. Electronic address: j.bras@ucl.ac.uk.

PMID: 26643944
PMCID: PMC4759606
DOI: 10.1016/j.neurobiolaging.2015.10.028

Abstract

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.

Keywords: Alzheimer's disease; Dementia with Lewy bodies; Genetic correlation; Parkinson's disease.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics*
Apolipoproteins E / genetics
Cohort Studies
Genetic Loci / genetics
Genome-Wide Association Study*
Humans
Lewy Body Disease / genetics*
Parkinson Disease / genetics*

Substances

Apolipoproteins E

Abstract

Publication types

MeSH terms

Substances

Grants and funding