SwePub
Tyck till om SwePub Sök här!
Sök i LIBRIS databas

  Extended search

onr:"swepub:oai:gup.ub.gu.se/263508"
 

Search: onr:"swepub:oai:gup.ub.gu.se/263508" > Investigating the g...

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist
  • Guerreiro, R.University of Aveiro,University College London (author)

Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/263508
  • https://gup.ub.gu.se/publication/263508URI
  • https://doi.org/10.1016/S1474-4422(17)30400-3DOI
  • https://lup.lub.lu.se/record/3db91543-ef1e-4af9-8603-3892a05ee40eURI

Supplementary language notes

  • Language:English

Part of subdatabase

Classification

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

Notes

  • Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson's disease, and Alzheimer's disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also only in participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2.40, 95% CI 2.14-2.70; p=1.05 x 10-48), SNCA (rs7681440; OR 0.73, 0.66-0.81; p=6.39 x 10(-10)), and GBA (rs35749011; OR 2.55, 1.88-3.46; p=1.78 x 10(-9)). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1.51, 1.27-1.79; p=2.32 x 10(-6)); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Ross, O. A.Mayo Clinic Florida,University of Oxford (author)
  • Kun-Rodrigues, C.University College London (author)
  • Hernandez, D. G.National Institutes of Health, United States,German Center for Neurodegenerative Diseases (DZNE), Bonn,Veterans Health Administration,University of California, San Diego (author)
  • Orme, T.University College London (author)
  • Eicher, J. D.Merck Sharp And Dohme Corp., US (author)
  • Shepherd, C. E.University of New South Wales (author)
  • Parkkinen, L.University of Oxford (author)
  • Darwent, L.University College London (author)
  • Heckman, M. G.Mayo Clinic Florida (author)
  • Scholz, S. W.National Institutes of Health, United States (author)
  • Troncoso, J. C.Johns Hopkins University School of Medicine,Autonomous University of Barcelona,CIBER Enfermedades Neurodegenerativas (CIBERNED) (author)
  • Pletnikova, O.Johns Hopkins University School of Medicine (author)
  • Ansorge, O. (author)
  • Clarimon, J.Washington University in St. Louis (author)
  • Lleo, A.CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona (author)
  • Morenas-Rodriguez, E.CIBER Enfermedades Neurodegenerativas (CIBERNED),Autonomous University of Barcelona (author)
  • Clark, L.Columbia University (author)
  • Honig, L. S.Columbia University,Pitié-Salpêtrière University Hospital (author)
  • Marder, K.Columbia University (author)
  • Lemstra, A.Amsterdam UMC - Vrije Universiteit Amsterdam (author)
  • Rogaeva, E.University of Toronto (author)
  • St George-Hyslop, P.University of Cambridge,University of Toronto,Autonomous University of Barcelona,Mutua De Terrassa Hospital (author)
  • Londos, ElisabetLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)pski-elo (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,University College London,Sahlgrenska University Hospital(Swepub:lu)med-hiz (author)
  • Barber, I.University of Nottingham (author)
  • Braae, A.University of Nottingham (author)
  • Brown, K.University of Nottingham (author)
  • Morgan, K.University of Nottingham (author)
  • Troakes, C.King's College London (author)
  • Al-Sarraj, S.King's College London (author)
  • Lashley, T.University College London (author)
  • Holton, J.University College London (author)
  • Compta, Y.University College London,University of Barcelona (author)
  • Van Deerlin, V.University of Pennsylvania (author)
  • Serrano, G. E.Banner Sun Health Research Institute (author)
  • Beach, T. G.Banner Sun Health Research Institute (author)
  • Lesage, S. (author)
  • Galasko, D. (author)
  • Masliah, E.National Institutes of Health, United States (author)
  • Santana, I.University of Coimbra (author)
  • Pastor, P. (author)
  • Diez-Fairen, M.Mutua De Terrassa Hospital,Autonomous University of Barcelona (author)
  • Aguilar, M.Autonomous University of Barcelona,Mutua De Terrassa Hospital (author)
  • Tienari, P. J.University of Helsinki,Helsinki University Central Hospital (author)
  • Myllykangas, L.Helsinki University Central Hospital,University of Helsinki Haartman Institute (author)
  • Oinas, M.Helsinki University Central Hospital,University of Helsinki (author)
  • Revesz, T.University College London (author)
  • Lees, A.University College London (author)
  • Boeve, B. F.Mayo Clinic Minnesota (author)
  • Petersen, R. C.Mayo Clinic Minnesota (author)
  • Ferman, T. J.Mayo Clinic Florida (author)
  • Escott-Price, V.Cardiff University (author)
  • Graff-Radford, N.Mayo Clinic Florida (author)
  • Cairns, N. J.Washington University in St. Louis (author)
  • Morris, J. C. (author)
  • Pickering-Brown, S.University of Manchester (author)
  • Mann, D.University of Manchester (author)
  • Halliday, G. M.University of New South Wales,University of Sydney (author)
  • Hardy, J.University College London (author)
  • Trojanowski, J. Q.University of Pennsylvania (author)
  • Dickson, D. W.Mayo Clinic Florida (author)
  • Singleton, A.National Institutes of Health, United States (author)
  • Stone, D. J.Merck Sharp And Dohme Corp., US (author)
  • Bras, J.University of Aveiro,University College London (author)
  • University of AveiroUniversity College London (creator_code:org_t)

Related titles

  • In:Lancet Neurology17:1, s. 64-741474-4422

Internet link

Find in a library

To the university's database

  • 1 of 1
  • Previous record
  • Next record
  •    To hitlist

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Close

Copy and save the link in order to return to this view