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  • Blokland, G. A. M. (author)

Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • Elsevier BV,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/306393
  • https://gup.ub.gu.se/publication/306393URI
  • https://doi.org/10.1016/j.biopsych.2021.02.972DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-197706URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:148701044URI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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

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  • Preisig, M. (author)
  • Schaefer, C. (author)
  • Smoller, J. W. (author)
  • Stefansson, K. (author)
  • Tiemeier, H. (author)
  • Uher, R. (author)
  • Völzke, H. (author)
  • Weissman, M. M. (author)
  • Werge, T. (author)
  • Lewis, C. M. (author)
  • Levinson, D. F. (author)
  • Børglum, A. D. (author)
  • Air, T. (author)
  • Völker, U. (author)
  • Bortolato, M. (author)
  • Bralten, J. (author)
  • Bulik, C. M. (author)
  • Burton, C. L. (author)
  • Carey, C. E. (author)
  • Davis, L. K. (author)
  • Duncan, L. E. (author)
  • Edenberg, H. J. (author)
  • Erdman, L. (author)
  • Faraone, S. V. (author)
  • Goldstein, J. M. (author)
  • Goleva, S. B. (author)
  • Guo, W. (author)
  • Hübel, C. (author)
  • Huckins, L. M. (author)
  • Khramtsova, E. A. (author)
  • Martin, J. (author)
  • Mathews, C. A. (author)
  • Petryshen, T. L. (author)
  • Robinson, E. (author)
  • Stahl, E. (author)
  • Stranger, B. E. (author)
  • Traglia, M. (author)
  • Walters, R. K. (author)
  • Weiss, L. A. (author)
  • Winham, S. J. (author)
  • Yao, Y. (author)
  • Skajaa, K. (author)
  • Nöthen, M. (author)
  • Owen, M. (author)
  • Yolken, R. H. (author)
  • Plath, N. (author)
  • Mill, J. (author)
  • Geschwind, D. (author)
  • Mortensen, P. B. (author)
  • Schizophrenia Working Group of the Psychiatric Genomics, Consortium (author)
  • Bipolar Disorder Working Group of the Psychiatric Genomics, Consortium (author)
  • Major Depressive Disorder Working Group of the Psychiatric Genomics, Consortium (author)
  • Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics, Consortium (author)
  • iPsych,, iPsych, (author)
  • Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

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  • In:Biological Psychiatry: Elsevier BV91:1, s. 102-1170006-32231873-2402

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Völzke, H.
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Lewis, C. M.
Levinson, D. F.
Børglum, A. D.
Air, T.
Völker, U.
Bortolato, M.
Bralten, J.
Bulik, C. M.
Burton, C. L.
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Davis, L. K.
Duncan, L. E.
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Martin, J.
Mathews, C. A.
Petryshen, T. L.
Robinson, E.
Stahl, E.
Stranger, B. E.
Traglia, M.
Walters, R. K.
Weiss, L. A.
Winham, S. J.
Yao, Y.
Skajaa, K.
Nöthen, M.
Owen, M.
Yolken, R. H.
Plath, N.
Mill, J.
Geschwind, D.
Schizophrenia Wo ...
Bipolar Disorder ...
Major Depressive ...
Sex Differences ...
iPsych,, iPsych
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Psychiatry
Articles in the publication
Biological Psych ...
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Umeå University
Karolinska Institutet

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