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Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia

Wen, J (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Trost, B (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
Engchuan, W (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
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Halvorsen, M (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Pallotto, LM (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
Mitina, A (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
Ancalade, N (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Farrell, M (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Backstrom, I (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
Guo, KY (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.
Pellecchia, G (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
Thiruvahindrapuram, B (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada.
Giusti-Rodriguez, P (författare)
Univ Florida, Dept Psychiat, Coll Med, Gainesville, FL 32610 USA.
Rosen, JD (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Li, Y (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
Won, HJ (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
Magnusson, PKE (författare)
Karolinska Institutet,Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
Gyllensten, Ulf B. (författare)
Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
Bassett, AS (författare)
Ctr Addict & Mental Hlth, Clin Genet Res Program, Toronto, ON M6J 1H4, Canada.;Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, Toronto, ON M6J 1H4, Canada.;Univ Hlth Network, Dalglish Family Clin Adults Delet Syndrome 22q 22, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada.;Univ Hlth Network, Toronto Gen Hosp, Res Inst, Toronto, ON M5G 2C4, Canada.;Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A8, Canada.
Hultman, CM (författare)
Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
Sullivan, PF (författare)
Karolinska Institutet,Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.;Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
Yuen, RKC (författare)
Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
Szatkiewicz, JP (författare)
Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
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Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA Hosp Sick Children, Genet & Genome Biol, Toronto, ON M5G 1X8, Canada.;Hosp Sick Children, Ctr Appl Genom, Toronto, ON M5G 1X8, Canada. (creator_code:org_t)
2022-11-16
2023
Engelska.
Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 28:21, s. 475-482
Relaterad länk:
https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
http://kipublication...
https://doi.org/10.1...
https://urn.kb.se/re...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2–20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Psykiatri (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Psychiatry (hsv//eng)

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