id:"swepub:oai:DiVA.org:umu-202575"
Sökning: id:"swepub:oai:DiVA.org:umu-202575" > Methylation in MAD1...
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
-
- Sokolov, Aleksandr V. (författare)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
-
- Manu, Diana-Maria (författare)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
-
- Nordberg, Didi O. T. (författare)
- Uppsala universitet,Funktionell farmakologi och neurovetenskap
- visa fler...
- visa färre...
- (creator_code:org_t)
- 2023-01-04
- 2023
- Engelska.
- Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 15:1
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Nyckelord
- Depression
- DNA methylation
- MAD1L1
- Suicide
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
- 1 av 1
- Föregående post
- Nästa post
- Till träfflistan
Hitta mer i SwePub
- Av författaren/redakt...
- Sokolov, Aleksan ...
- Manu, Diana-Mari ...
- Nordberg, Didi O ...
- Boström, Adrian ...
- Jokinen, Jussi
- Schiöth, Helgi B ...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Klinisk medicin
- och Psykiatri
-
- MEDICIN OCH HÄLSOVETENSKAP
- MEDICIN OCH HÄLS ...
- och Medicinska och f ...
- och Medicinsk geneti ...
- Artiklar i publikationen
- Clinical Epigene ...
- Av lärosätet
- Umeå universitet
- Uppsala universitet
- Karolinska Institutet
Sök utanför SwePub
- Sök vidare i:
- Google Book Search
- Google Scholar
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.
- Copyright © LIBRIS - Nationella bibliotekssystem
- LIBRIS.kb.se
