Investigating the potential impact of PCSK9-inhibitors on mood disorders using eQTL-based Mendelian randomization

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: WFRF:( DM) > (2020-2024) > Investigating the p...

LIBRIS Formathandbok (Information om MARC21)

Fältnamn	Indikatorer	Metadata
000		02986naa a2200337 4500
001		oai:prod.swepub.kib.ki.se:151906170
003		SwePub
008		240701s2022 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1519061702 URI
024	7	a https://doi.org/10.1371/journal.pone.02793812 DOI
040		a (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Aman, A4 aut
245	1 0	a Investigating the potential impact of PCSK9-inhibitors on mood disorders using eQTL-based Mendelian randomization
264		c 2022-12-29
264	1	b Public Library of Science (PLoS),c 2022
520		a Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5–0.03), and neuroticism score (p-value range = 2.9x10-5–0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.
700	1	a Slob, EAW4 aut
700	1	a Ward, J4 aut
700	1	a Cullen, B4 aut
700	1	a Graham, N4 aut
700	1	a Lyall, DM4 aut
700	1	a Sattar, N4 aut
700	1	a Strawbridge, RJu Karolinska Institutet4 aut
710	2	a Karolinska Institutet4 org
773	0	t PloS oned : Public Library of Science (PLoS)g 17:12, s. e0279381-q 17:12<e0279381-x 1932-6203
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:151906170
856	4 8	u https://doi.org/10.1371/journal.pone.0279381

Hitta via bibliotek

PloS one (Sök värdpublikationen i LIBRIS)

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...: Aman, A; Slob, EAW; Ward, J; Cullen, B; Graham, N; Lyall, DM; visa fler...; Sattar, N; Strawbridge, RJ; visa färre...

Artiklar i publikationen: PloS one

Av lärosätet: Karolinska Institutet

Sök utanför SwePub

Sök vidare i:: Google; 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.

LIBRIS.kb.se