Sökning: WFRF:(Zandi P.) > Sex-Dependent Share...
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000 | 25068naa a2207429 4500 | |
001 | oai:gup.ub.gu.se/306393 | |
003 | SwePub | |
008 | 240528s2022 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:umu-197706 | |
009 | oai:prod.swepub.kib.ki.se:148701044 | |
024 | 7 | a https://gup.ub.gu.se/publication/3063932 URI |
024 | 7 | a https://doi.org/10.1016/j.biopsych.2021.02.9722 DOI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1977062 URI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1487010442 URI |
040 | a (SwePub)gud (SwePub)umud (SwePub)ki | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Blokland, G. A. M.4 aut |
245 | 1 0 | a Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders |
264 | 1 | b Elsevier BV,c 2022 |
520 | a Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Psykiatri0 (SwePub)302152 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Psychiatry0 (SwePub)302152 hsv//eng |
653 | a Bipolar disorder | |
653 | a Genome-wide association study | |
653 | a Genotype-by-sex interaction | |
653 | a Major depressive disorder | |
653 | a Schizophrenia | |
653 | a Sex differences | |
653 | a Bipolar disorder | |
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700 | 1 | a Landén, Mikael,d 1966u Gothenburg University,Göteborgs universitet,Karolinska Institutet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xlandt |
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700 | 1 | a Landén, Mikael,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry4 aut0 (Swepub:gu)xlandt |
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773 | 0 | t Biological Psychiatryd : Elsevier BVg 91:1, s. 102-117q 91:1<102-117x 0006-3223x 1873-2402 |
856 | 4 | u https://www.biorxiv.org/content/biorxiv/early/2021/01/30/2020.08.13.249813.full.pdf |
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