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dc.contributor.authorHindley, Guy Frederick Lanyon
dc.contributor.authorO'Connell, Kevin Sean
dc.contributor.authorRahman, Zillur
dc.contributor.authorFrei, Oleksandr
dc.contributor.authorBahrami, Shahram
dc.contributor.authorShadrin, Alexey
dc.contributor.authorHøegh, Margrethe Collier
dc.contributor.authorCheng, Weiqiu
dc.contributor.authorKaradag, Naz
dc.contributor.authorLin, Aihua
dc.contributor.authorRødevand, Linn
dc.contributor.authorFan, Chun C.
dc.contributor.authorDjurovic, Srdjan
dc.contributor.authorLagerberg, Trine Vik
dc.contributor.authorDale, Anders
dc.contributor.authorSmeland, Olav Bjerkehagen
dc.contributor.authorAndreassen, Ole
dc.description.abstractRecent genome-wide association studies of mood instability (MOOD) have found significant positive genetic correlation with major depression (DEP) and weak correlations with other psychiatric disorders. We investigated the polygenic overlap between MOOD and psychiatric disorders beyond genetic correlation to better characterize putative shared genetic determinants. GWAS summary statistics for schizophrenia (SCZ, n = 105,318), bipolar disorder (BIP, n = 413,466), DEP (n = 450,619), attention-deficit hyperactivity disorder (ADHD, n = 53,293), and MOOD (n = 363,705) were analyzed using the bivariate causal mixture model and conjunctional false discovery rate methods. MOOD correlated positively with all psychiatric disorders, but with wide variation in strength (rg = 0.10–0.62). Of 10.4 K genomic variants influencing MOOD, 4 K–9.4 K influenced psychiatric disorders. Furthermore, MOOD was jointly associated with DEP at 163 loci, SCZ at 110, BIP at 60 and ADHD at 25. Fifty-three jointly associated loci were overlapping across two or more disorders, seven of which had discordant effect directions on psychiatric disorders. Genes mapped to loci associated with MOOD and all four disorders were enriched in a single gene-set, “synapse organization.” The extensive polygenic overlap indicates shared molecular underpinnings across MOOD and psychiatric disorders. However, distinct patterns of genetic correlation and effect directions may relate to differences in the core clinical features of each disorder.en_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleThe shared genetic basis of mood instability and psychiatric disorders: A cross-trait genome-wide association analysisen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2022 the authorsen_US
dc.source.journalAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen_US
dc.identifier.citationAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2022, 189 (6), 207-218.en_US

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