Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
Visa övriga samt affilieringar
2021 (Engelska)Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, nr 12, s. 1636-1648Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2021. Vol. 53, nr 12, s. 1636-1648
Nationell ämneskategori
Neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-191609DOI: 10.1038/s41588-021-00973-1ISI: 000727387900007PubMedID: 34873335Scopus ID: 2-s2.0-85122277130OAI: oai:DiVA.org:umu-191609DiVA, id: diva2:1630308
Tillgänglig från: 2022-01-20 Skapad: 2022-01-20 Senast uppdaterad: 2022-01-20Bibliografiskt granskad

Open Access i DiVA

fulltext(9080 kB)82 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 9080 kBChecksumma SHA-512
fee9023765e79610b610ed93110cc5a5a4054c918aaa6a4431f75adb685aae3655f618228d94fe37d60a5bb773ebe0be37e0aeab21d766a618691c672951787d
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltextPubMedScopus

Person

Nordin, AngelicaAndersen, Peter M.

Sök vidare i DiVA

Av författaren/redaktören
van Rheenen, WouterDeelen, PatrickCooper-Knock, JohnathanGromicho, MartaHardy, JohnLauria, GiuseppeCereda, CristinaNordin, AngelicaVourc'h, PatrickRoss, Jay P.Wood, Nicholas W.Cotelli, Maria SofiaPensato, VivianaSteinbach, RobertSteyn, Frederik J.Pinto, SusanaAndersen, Peter M.Wray, Naomi R.Van Damme, Philip
Av organisationen
Neurovetenskaper
I samma tidskrift
Nature Genetics
Neurologi

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 82 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
pubmed
urn-nbn

Altmetricpoäng

doi
pubmed
urn-nbn
Totalt: 167 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf