Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

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MARC

Bryois, J.Karolinska Institutet (author)

Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

Article/chapterEnglish2020

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2020-04-27
Springer Science and Business Media LLC,2020

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LIBRIS-ID:oai:gup.ub.gu.se/296136
https://gup.ub.gu.se/publication/296136URI
https://doi.org/10.1038/s41588-020-0610-9DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:143572790URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Neurovetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Neurosciences hsv//eng
hemoglobin A1c
RNA
Article
autism
bipolar disorder
body mass
cells by body anatomy
cerebrovascular accident
cholinergic nerve cell
coronary artery disease
disease exacerbation
educational status
gene expression
genetic association
genetic correlation
genetic identification
genome-wide association study
glycemic control
human
human tissue
inflammatory bowel disease
mental disease
monoamine nerve cell
neurologic disease
neurosis
non insulin dependent diabetes mellitus
nonhuman
oligodendroglia
Parkinson disease
parkinsonism
priority journal
RNA sequencing
schizophrenia
single cell RNA seq
transcriptomics
upregulation
waist hip ratio

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Skene, N. G. (author)
Hansen, T. F. (author)
Kogelman, L. J. A. (author)
Watson, H. J. (author)
Liu, Z. (author)
Adan, Roger A. H.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xadaro (author)
Alfredsson, L. (author)
Ando, T. (author)
Andreassen, O. (author)
Baker, J. (author)
Bergen, A. (author)
Berrettini, W. (author)
Birgegård, A. (author)
Boden, J. (author)
Boehm, I. (author)
Boni, C. (author)
Boraska Perica, V. (author)
Brandt, H. (author)
Breen, G. (author)
Bryois, J. (author)
Buehren, K. (author)
Bulik, C. (author)
Burghardt, R. (author)
Cassina, M. (author)
Cichon, S. (author)
Clementi, M. (author)
Coleman, J. (author)
Cone, R. (author)
Courtet, P. (author)
Crawford, S. (author)
Crow, S. (author)
Crowley, J. (author)
Danner, U. (author)
Davis, O. (author)
de Zwaan, M. (author)
Dedoussis, G. (author)
Degortes, D. (author)
DeSocio, J. (author)
Dick, D. (author)
Dikeos, D. (author)
Dina, C. (author)
Dmitrzak-Weglarz, M. (author)
Docampo Martinez, E. (author)
Duncan, L. (author)
Egberts, K. (author)
Ehrlich, S. (author)
Escaramís, G. (author)
Esko, T. (author)
Estivill, X. (author)
Farmer, A. (author)
Favaro, A. (author)
Fernández-Aranda, F. (author)
Fichter, M. (author)
Fischer, K. (author)
Föcker, M. (author)
Foretova, L. (author)
Forstner, A. (author)
Forzan, M. (author)
Franklin, C. (author)
Gallinger, S. (author)
Gaspar, H. (author)
Giegling, I. (author)
Giuranna, J. (author)
Giusti-Rodríquez, P. (author)
Gonidakis, F. (author)
Gordon, S. (author)
Gorwood, P. (author)
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Grove, J. (author)
Guillaume, S. (author)
Guo, Y. (author)
Hakonarson, H. (author)
Halmi, K. (author)
Hanscombe, K. (author)
Hatzikotoulas, K. (author)
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Helder, S. (author)
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Herpertz-Dahlmann, B. (author)
Herzog, W. (author)
Hinney, A. (author)
Horwood, L. J. (author)
Hübel, C. (author)
Huckins, L. (author)
Hudson, J. (author)
Imgart, H. (author)
Inoko, H. (author)
Janout, V. (author)
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Johnson, C. (author)
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Julià, A. (author)
Juréus, A. (author)
Kalsi, G. (author)
Kaminská, D. (author)
Kaplan, A. (author)
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Karwautz, A. (author)
Kas, M. (author)
Kaye, W. (author)
Kennedy, J. (author)
Kennedy, M. (author)
Keski-Rahkonen, A. (author)
Kiezebrink, K. (author)
Kim, Y. R. (author)
Kirk, K. (author)
Klareskog, L. (author)
Klump, K. (author)
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La Via, M. (author)
Landén, M. (author)
Larsen, J. (author)
Le Hellard, S. (author)
Leppä, V. (author)
Levitan, R. (author)
Li, D. (author)
Lichtenstein, P. (author)
Lilenfeld, L. (author)
Lin, B. D. (author)
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Magistretti, P. (author)
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Mannik, K. (author)
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Marshall, C. (author)
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Mattheisen, M. (author)
Mattingsdal, M. (author)
McDevitt, S. (author)
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Monteleone, P. (author)
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Olsen, C. (author)
Ophoff, R. (author)
O’Toole, J. (author)
Padyukov, L. (author)
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Rotondo, A. (author)
Rujescu, D. (author)
Rybakowski, F. (author)
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Slof-Op ‘t Landt, M. (author)
Slopien, A. (author)
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Strober, M. (author)
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Neale, B. M. (author)
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Posthuma, D. (author)
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Terwindt, G. (author)
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Zhao, H. (author)
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Alipanahi, B. (author)
Auton, A. (author)
Bell, R. (author)
Bryc, K. (author)
Elson, S. (author)
Fontanillas, P. (author)
Furlotte, N. (author)
Heilbron, K. (author)
Hinds, D. (author)
Huber, K. (author)
Kleinman, A. (author)
Litterman, N. (author)
McCreight, J. (author)
McIntyre, M. (author)
Mountain, J. (author)
Noblin, E. (author)
Northover, C. (author)
Pitts, S. (author)
Sathirapongsasuti, J. (author)
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Tian, C. (author)
Tung, J. (author)
Vacic, V. (author)
Wilson, C. (author)
Brueggeman, L. (author)
Breen, G. (author)
Bulik, C. M. (author)
Arenas, E. (author)
Hjerling-Leffler, J. (author)
Sullivan, P. F. (author)
Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi (creator_code:org_t)

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By the author/editor: Bryois, J.; Skene, N. G.; Hansen, T. F.; Kogelman, L. J. ...; Watson, H. J.; Liu, Z.; show more...; Adan, Roger A. H ...; Alfredsson, L.; Ando, T.; Andreassen, O.; Baker, J.; Bergen, A.; Berrettini, W.; Birgegård, A.; Boden, J.; Boehm, I.; Boni, C.; Boraska Perica, ...; Brandt, H.; Breen, G.; Buehren, K.; Bulik, C.; Burghardt, R.; Cassina, M.; Cichon, S.; Clementi, M.; Coleman, J.; Cone, R.; Courtet, P.; Crawford, S.; Crow, S.; Crowley, J.; Danner, U.; Davis, O.; de Zwaan, M.; Dedoussis, G.; Degortes, D.; DeSocio, J.; Dick, D.; Dikeos, D.; Dina, C.; Dmitrzak-Weglarz ...; Docampo Martinez ...; Duncan, L.; Egberts, K.; Ehrlich, S.; Escaramís, G.; Esko, T.; Estivill, X.; Farmer, A.; Favaro, A.; Fernández-Aranda ...; Fichter, M.; Fischer, K.; Föcker, M.; Foretova, L.; Forstner, A.; Forzan, M.; Franklin, C.; Gallinger, S.; Gaspar, H.; Giegling, I.; Giuranna, J.; Giusti-Rodríquez ...; Gonidakis, F.; Gordon, S.; Gorwood, P.; Gratacos Mayora, ...; Grove, J.; Guillaume, S.; Guo, Y.; Hakonarson, H.; Halmi, K.; Hanscombe, K.; Hatzikotoulas, K ...; Hauser, J.; Hebebrand, J.; Helder, S.; Henders, A.; Herms, S.; Herpertz-Dahlman ...; Herzog, W.; Hinney, A.; Horwood, L. J.; Hübel, C.; Huckins, L.; Hudson, J.; Imgart, H.; Inoko, H.; Janout, V.; Jiménez-Murcia, ...; Johnson, C.; Jordan, J.; Julià, A.; Juréus, A.; Kalsi, G.; Kaminská, D.; Kaplan, A.; Kaprio, J.; Karhunen, L.; Karwautz, A.; Kas, M.; Kaye, W.; Kennedy, J.; Kennedy, M.; Keski-Rahkonen, ...; Kiezebrink, K.; Kim, Y. R.; Kirk, K.; Klareskog, L.; Klump, K.; Knudsen, G. P.; La Via, M.; Landén, M.; Larsen, J.; Le Hellard, S.; Leppä, V.; Levitan, R.; Li, D.; Lichtenstein, P.; Lilenfeld, L.; Lin, B. D.; Lissowska, J.; Luykx, J.; Magistretti, P.; Maj, M.; Mannik, K.; Marsal, S.; Marshall, C.; Martin, N.; Mattheisen, M.; Mattingsdal, M.; McDevitt, S.; McGuffin, P.; Medland, S.; Metspalu, A.; Meulenbelt, I.; Micali, N.; Mitchell, J.; Mitchell, K.; Monteleone, P.; Monteleone, A. M ...; Montgomery, G.; Mortensen, P. B.; Munn-Chernoff, M ...; Nacmias, B.; Navratilova, M.; Norring, C.; Ntalla, I.; Olsen, C.; Ophoff, R.; O’Toole, J.; Padyukov, L.; Palotie, A.; Pantel, J.; Papezova, H.; Parker, R.; Pearson, J.; Pedersen, N.; Petersen, L.; Pinto, D.; Purves, K.; Rabionet, R.; Raevuori, A.; Ramoz, N.; Reichborn-Kjenne ...; Ricca, V.; Ripatti, S.; Ripke, S.; Ritschel, F.; Roberts, M.; Rotondo, A.; Rujescu, D.; Rybakowski, F.; Santonastaso, P.; Scherag, A.; Scherer, S.; Schmidt, U.; Schork, N.; Schosser, A.; Seitz, J.; Slachtova, L.; Slagboom, P. E.; Slof-Op ‘t Landt ...; Slopien, A.; Sorbi, S.; Strober, M.; Stuber, G.; Sullivan, P.; Świątkowska, B.; Szatkiewicz, J.; Tachmazidou, I.; Tenconi, E.; Thornton, L.; Tortorella, A.; Tozzi, F.; Treasure, J.; Tsitsika, A.; Tyszkiewicz-Nwaf ...; Tziouvas, K.; van Elburg, A.; van Furth, E.; Wade, T.; Wagner, G.; Walton, E.; Watson, H.; Werge, T.; Whiteman, D.; Widen, E.; Woodside, D. B.; Yao, S.; Yilmaz, Z.; Zeggini, E.; Zerwas, S.; Zipfel, S.; Anttila, V.; Artto, V.; Belin, A. C.; de Boer, I.; Boomsma, D. I.; Børte, S.; Chasman, D. I.; Cherkas, L.; Christensen, A. ...; Cormand, B.; Cuenca-Leon, E.; Davey-Smith, G.; Dichgans, M.; van Duijn, C.; Esserlind, A. L.; Ferrari, M.; Frants, R. R.; Freilinger, T.; Furlotte, N.; Gormley, P.; Griffiths, L.; Hamalainen, E.; Hiekkala, M.; Ikram, M. A.; Ingason, A.; Järvelin, M. R.; Kajanne, R.; Kallela, M.; Kaunisto, M.; Kubisch, C.; Kurki, M.; Kurth, T.; Launer, L.; Lehtimaki, T.; Lessel, D.; Ligthart, L.; Litterman, N.; Maagdenberg, A.; Macaya, A.; Malik, R.; Mangino, M.; McMahon, G.; Muller-Myhsok, B ...; Neale, B. M.; Northover, C.; Nyholt, D. R.; Olesen, J.; Palta, P.; Pedersen, L.; Posthuma, D.; Pozo-Rosich, P.; Pressman, A.; Raitakari, O.; Schürks, M.; Sintas, C.; Stefansson, K.; Stefansson, H.; Steinberg, S.; Strachan, D.; Terwindt, G.; Vila-Pueyo, M.; Wessman, M.; Winsvold, B. S.; Zhao, H.; Zwart, J. A.; Agee, M.; Alipanahi, B.; Auton, A.; Bell, R.; Bryc, K.; Elson, S.; Fontanillas, P.; Heilbron, K.; Hinds, D.; Huber, K.; Kleinman, A.; McCreight, J.; McIntyre, M.; Mountain, J.; Noblin, E.; Pitts, S.; Sathirapongsasut ...; Sazonova, O.; Shelton, J.; Shringarpure, S.; Tian, C.; Tung, J.; Vacic, V.; Wilson, C.; Brueggeman, L.; Bulik, C. M.; Arenas, E.; Hjerling-Leffler ...; Sullivan, P. F.; show less...

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